RNA-binding proteins (RBPs) are of fundamental importance for post-transcriptional gene regulation and protein synthesis. They are required for pre-mRNA processing and for RNA transport, degradation and translation into protein, and can regulate every step in the life cycle of their RNA targets. In addition, RBP function can be modulated by RNA binding. RBPs also participate in the formation of ribonucleoprotein complexes that build up macromolecular machineries such as the ribosome and spliceosome. Although most research has focused on mRNA-binding proteins, non-coding RNAs are also regulated and sequestered by RBPs. Functional defects and changes in the expression levels of RBPs have been implicated in numerous diseases, including neurological disorders, muscular atrophy and cancers. RBPs also contribute to a wide spectrum of kidney disorders. For example, human antigen R has been reported to have a renoprotective function in acute kidney injury (AKI) but might also contribute to the development of glomerulosclerosis, tubulointerstitial fibrosis and diabetic kidney disease (DKD), loss of bicaudal C is associated with cystic kidney diseases and Y-box binding protein 1 has been implicated in the pathogenesis of AKI, DKD and glomerular disorders. Increasing data suggest that the modulation of RBPs and their interactions with RNA targets could be promising therapeutic strategies for kidney diseases.
The human genome contains more than 1,000 RNA-binding proteins (RBPs), which are involved in every step of the RNA life cycle and have a major impact on cellular biology.
RBPs have been shown to have roles in tubular and glomerular kidney diseases, including acute kidney injury (AKI), chronic kidney disease, kidney fibrosis, polycystic kidney disease (PKD), diabetic kidney disease and glomerulonephritis.
RBPs can have both protective and pathogenic roles in kidney diseases; for example, two of the best studied RBPs — HuR and YBX1 — ameliorate damage in AKI but promote kidney fibrosis.
The role of RBPs in kidney disorders is conserved throughout evolution; for example, mutations in BICC1 lead to a cystic phenotype of the Malpigian tubules in Drosophila melanogaster and are associated with PKD in vertebrates.
Environmental changes that are associated with renal pathophysiology, such as hypo-osmolality or hypoxia, can modulate RNA–protein interactions.
RNA–protein interactions can be inhibited and are potential therapeutic targets for various kidney diseases.
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Kapeli, K., Martinez, F. J. & Yeo, G. W. Genetic mutations in RNA-binding proteins and their roles in ALS. Hum. Genet. 136, 1193–1214 (2017).
Lukong, K. E., Chang, K. W., Khandjian, E. W. & Richard, S. RNA-binding proteins in human genetic disease. Trends Genet. 24, 416–425 (2008).
Gebauer, F., Schwarzl, T., Valcárcel, J. & Hentze, M. W. RNA-binding proteins in human genetic disease. Nat. Rev. Genet. 22, 185–198 (2021).
Gerstberger, S., Hafner, M. & Tuschl, T. A census of human RNA-binding proteins. Nat. Rev. Genet. 15, 829–845 (2014).
Singh, G., Pratt, G., Yeo, G. W. & Moore, M. J. The clothes make the mRNA: past and present trends in mRNP fashion. Annu. Rev. Biochem. 84, 325–354 (2015).
Ho, J. J. D. et al. A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism. Nat. Commun. 11, 1–16 (2020).
Dassi, E. Handshakes and fights: the regulatory interplay of RNA-binding proteins. Front. Mol. Biosci. 4, 67 (2017).
Vázquez-Chantada, M. et al. HuR/Methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology 138, 1943–1953 (2010).
Sun, S. et al. Autotaxin expression is regulated at the post-transcriptional level by the RNA-binding proteins HuR and AUF1. J. Biol. Chem. 291, 25823–25836 (2016).
Poganik, J. R. et al. Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. FASEB J. 33, 14636–14652 (2019).
Wang, J., Hjelmeland, A. B., Nabors, L. B. & King, P. H. Anti-cancer effects of the HuR inhibitor, MS-444, in malignant glioma cells. Cancer Biol. Ther. 20, 979–988 (2019).
García-Mauriño, S. M. et al. RNA binding protein regulation and cross-talk in the control of AU-rich mRNA fate. Front. Mol. Biosci. 4, 71 (2017).
Baltz, A. G. et al. The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol. Cell 46, 674–690 (2012). Landmark study implementing RNA-interactome capture based on 4-SU labelling and UVA crosslinking.
Castello, A. et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149, 1393–1406 (2012). Landmark study implementing RNA-interactome capture based on UVC crosslinking.
Conrad, T. et al. Serial interactome capture of the human cell nucleus. Nat. Commun. 7, 11212 (2016).
Licatalosi, D. D. et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464–469 (2008).
Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129–141 (2010).
König, J. et al. ICLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17, 909–915 (2010).
Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods 13, 508–514 (2016).
Sharma, D. et al. The kinetic landscape of an RNA-binding protein in cells. Nature 591, 152–156 (2021).
Caudron-Herger, M., Jansen, R. E., Wassmer, E. & Diederichs, S. RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions. Nucleic Acids Res. 49, D425–D436 (2020). Minable tool for obtaining an insight into current knowledge on RBPs and their function.
Cléry, A., Blatter, M. & Allain, F. H. T. RNA recognition motifs: boring? Not quite. Curr. Opin. Struct. Biol. 18, 290–298 (2008).
Linder, P. & Jankowsky, E. From unwinding to clamping-the DEAD box RNA helicase family. Nat. Rev. Mol. Cell Biol. 12, 505–516 (2011).
Valverde, R., Edwards, L. & Regan, L. Structure and function of KH domains. FEBS J. 275, 2712–2726 (2008).
Beckmann, B. M. et al. The RNA-binding proteomes from yeast to man harbour conserved enigmRBPs. Nat. Commun. 6, 10127 (2015). Extensive analysis of RBPomes in several species showing the abundance of RBPs lacking a classical RNA-binding domain, so-called enigmRBPs.
Hentze, M. W., Castello, A., Schwarzl, T. & Preiss, T. A brave new world of RNA-binding proteins. Nat. Rev. Mol. Cell Biol. 19, 327–341 (2018).
Esmaillie, R. et al. Activation of hypoxia-inducible factor signaling modulates the RNA protein interactome in Caenorhabditis elegans. iScience 22, 466–476 (2019).
Ignarski, M. et al. The RNA-protein interactome of differentiated kidney tubular epithelial cells. J. Am. Soc. Nephrol. 30, 564–576 (2019). The first global RBPome in cultured renal tubule cells and its modulation by hypoxia.
Hämmerle, M. et al. Posttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). Hepatology 58, 1703–1712 (2013).
Wang, I. K. et al. The functional interplay of lncRNA EGOT and HuR regulates hypoxia-induced autophagy in renal tubular cells. J. Cell. Biochem. 121, 4522–4534 (2020).
Fasolo, F. et al. The RNA-binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs. FASEB J. 33, 13572–13589 (2019).
Wahl, M. C., Will, C. L. & Lührmann, R. The spliceosome: design principles of a dynamic RNP machine. Cell 136, 701–718 (2009).
Wende, W., Friedhoff, P. & Sträßer, K. Mechanism and regulation of co-transcriptional mRNP assembly and nuclear mRNA export. Adv. Exp. Med. Biol. 1203, 1–31 (2019).
Rissland, O. S. The organization and regulation of mRNA–protein complexes. Wiley Interdiscip. Rev. RNA 8, e1369 (2017).
Harvey, R. F. et al. Trans-acting translational regulatory RNA binding proteins. Wiley Interdiscip. Rev. RNA 9, e1465 (2018).
Ivanov, P., Kedersha, N. & Anderson, P. Stress granules and processing bodies in translational control. Cold Spring Harb. Perspect. Biol. 11, a032813 (2019).
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).
Darling, A. L., Liu, Y., Oldfield, C. J. & Uversky, V. N. Intrinsically disordered proteome of human membrane-less organelles. Proteomics 18, e1700193 (2018).
Wang, S., Kwon, S.-H., Su, Y., Dong, Z. & Norwood, C. Stress granules are formed in renal proximal tubular cells during metabolic stress and ischemic injury for cell survival. Am. J. Physiol. Renal Physiol. 317, 116–123 (2019).
Estrada Mallarino, L. et al. Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules. Sci. Rep. 10, 15954 (2020).
Huang, B. & Zhang, R. Regulatory non-coding RNAs: revolutionizing the RNA world. Mol. Biol. Rep. 41, 3915–3923 (2014).
Matera, A. G. & Wang, Z. A day in the life of the spliceosome. Nat. Rev. Mol. Cell Biol. 15, 108–121 (2014).
Matera, A. G., Terns, R. M. & Terns, M. P. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8, 209–220 (2007).
Schimmel, P. RNA processing and modifications: the emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis. Nat. Rev. Mol. Cell Biol. 19, 45–58 (2018).
Kaiser, R. W. J. et al. A protein-RNA interaction atlas of the ribosome biogenesis factor AATF. Sci. Rep. 9, 11071 (2019).
Klinge, S. & Woolford, J. L. Ribosome assembly coming into focus. Nat. Rev. Mol. Cell Biol. 20, 116–131 (2019).
Olina, A. V., Kulbachinskiy, A. V., Aravin, A. A. & Esyunina, D. M. Argonaute proteins and mechanisms of RNA interference in eukaryotes and prokaryotes. Biochemistry 83, 483–497 (2018).
Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nat. Rev. Genet. 10, 94–108 (2009).
Kristensen, L. S. et al. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet. 20, 675–691 (2019).
Yao, R. W., Wang, Y. & Chen, L. L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 21, 542–551 (2019).
Sun, X., Haider Ali, M. S. S. & Moran, M. The role of interactions of long non-coding RNAs and heterogeneous nuclear ribonucleoproteins in regulating cellular functions. Biochem. J. 474, 2925–2935 (2017).
Kazimierczyk, M., Kasprowicz, M. K., Kasprzyk, M. E. & Wrzesinski, J. Human long noncoding RNA interactome: detection, characterization and function. Int. J. Mol. Sci. 21, 1027 (2020).
Copsey, A. C. et al. The helicase, DDX3X, interacts with poly(A)-binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading. Biochem. J. 474, 3109–3120 (2017).
Johnsen, M. et al. The integrated RNA landscape of renal preconditioning against ischemia-reperfusion injury. J. Am. Soc. Nephrol. 31, 716–730 (2020).
Colombrita, C., Silani, V. & Ratti, A. ELAV proteins along evolution: back to the nucleus? Mol. Cell. Neurosci. 56, 447–455 (2013).
De Toeuf, B. et al. ARE-mediated decay controls gene expression and cellular metabolism upon oxygen variations. Sci. Rep. 8, 5211 (2018).
Brennan, C. M. & Steitz, J. A. HuR and mRNA stability. Cell. Mol. Life Sci. 58, 266–277 (2001).
Hinman, M. N. & Lou, H. Diverse molecular functions of Hu proteins. Cell. Mol. Life Sci. 65, 3168–3181 (2008).
Jonas, K., Calin, G. A. & Pichler, M. RNA-binding proteins as important regulators of long non-coding RNAs in cancer. Int. J. Mol. Sci. 21, 2969 (2020).
Abdelmohsen, K. et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol. 14, 361–369 (2017).
Li, X.-X. et al. Interaction between HuR and circPABPN1 modulates autophagy in the intestinal epithelium by altering ATG16L1 translation. Mol. Cell. Biol. 40, e00492–19 (2020).
Grammatikakis, I., Abdelmohsen, K. & Gorospe, M. Posttranslational control of HuR function. RNA 8, 10.1002/wrna.1372 (2017).
Jeyaraj, S., Dakhlallah, D., Mill, S. R. & Lee, B. S. HuR stabilizes vacuolar H+-translocating ATPase mRNA during cellular energy depletion. J. Biol. Chem. 280, 37957–37964 (2005).
Jeyaraj, S. C., Dakhlallah, D., Hill, S. R. & Lee, B. S. Expression and distribution of HuR during ATP depletion and recovery in proximal tubule cells. Am. J. Physiol. Renal Physiol. 291, F1255–F1263 (2006).
Jeyaraj, S. C., Singh, M., Ayupova, D. A., Govindaraju, S. & Lee, B. S. Transcriptional control of human antigen R by bone morphogenetic protein. J. Biol. Chem. 285, 4432–4440 (2010).
Govindaraju, S. & Lee, B. S. Krüppel-like factor 8 is a stress-responsive transcription factor that regulates expression of HuR. Cell. Physiol. Biochem. 34, 519–532 (2014).
Ayupova, D. A., Singh, M., Leonard, E. C., Basile, D. P. & Lee, B. S. Expression of the RNA-stabilizing protein HuR in ischemia-reperfusion injury of rat kidney. Am. J. Physiol. Renal Physiol. 297, F95–F105 (2009).
Singh, M., Martinez, A. R., Govindaraju, S. & Lee, B. S. HuR inhibits apoptosis by amplifying Akt signaling through a positive feedback loop. J. Cell. Physiol. 228, 182–189 (2013).
Jiang, M., Liu, K., Luo, J. & Dong, Z. Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. Am. J. Pathol. 176, 1181–1192 (2010).
Jiang, M. et al. Autophagy in proximal tubules protects against acute kidney injury. Kidney Int. 82, 1271–1283 (2012).
Palanisamy, K. et al. RNA-binding protein, human antigen R regulates hypoxia-induced autophagy by targeting ATG7/ATG16L1 expressions and autophagosome formation. J. Cell. Physiol. 234, 7448–7458 (2019).
Bolisetty, S., Zarjou, A. & Agarwal, A. Heme oxygenase 1 as a therapeutic target in acute kidney injury. Am. J. Kidney Dis. 69, 531–545 (2017).
Li, S. et al. Hyperhomocysteinemia accelerates acute kidney injury to chronic kidney disease progression by downregulating heme oxygenase-1 expression. Antioxid. Redox Signal. 30, 1635–1650 (2019).
Long, Y. & Nie, J. Homocysteine in renal injury. Kidney Dis. 2, 80–87 (2016).
Nishiyama, H. et al. A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. J. Cell Biol. 137, 898–908 (1997).
Zhu, X., Bührer, C. & Wellmann, S. Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold. Cell. Mol. Life Sci. 73, 3839–3859 (2016).
Peng, Y. et al. Maternal cold inducible RNA binding protein is required for embryonic kidney formation in Xenopus laevis. FEBS Lett. 482, 37–43 (2000).
Cen, C. et al. Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion. Surgery 160, 473–483 (2016).
McGinn, J. et al. The protective effect of a short peptide derived from cold-inducible RNA-binding protein in renal ischemia-reperfusion injury. Shock 49, 269–276 (2018).
Zhang, F., Brenner, M., Yang, W. L. & Wang, P. A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice. Sci. Rep. 8, 3052 (2018).
Xia, Z. et al. Mild hypothermia protects renal function in ischemia-reperfusion kidney: an experimental study in mice. Transplant. Proc. 50, 3816–3821 (2018).
Yu, L., Gu, T., Liu, Y., Jiang, X. & Shi, E. Cold-inducible ribonucleic acid-binding protein attenuates acute kidney injuries after deep hypothermic circulatory arrest in rats. Interact. Cardiovasc. Thorac. Surg. 26, 124–130 (2018).
Zuo, Z. et al. Mechanisms and functions of mitophagy and potential roles in renal disease. Front. Physiol. 11, 935 (2020).
Perry, H. M. et al. Dynamin-related protein 1 deficiency promotes recovery from AKI. J. Am. Soc. Nephrol. 29, 194–206 (2018).
Wang, J. et al. Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury. Cell Biol. Toxicol. 36, 365–378 (2020).
D’Amico, D. et al. The RNA-binding protein PUM2 impairs mitochondrial dynamics and mitophagy during aging. Mol. Cell 73, 775–787.e10 (2019).
Goodarzi, H. et al. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 161, 790–802 (2015).
Wu, S. L. et al. Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme. Nucleic Acids Res. 43, 8516–8528 (2015).
Mordovkina, D. et al. Y-box binding proteins in mRNP assembly, translation, and stability control. Biomolecules 10, 591 (2020).
Yong, W. et al. The role of YB1 in renal cell carcinoma cell adhesion. Int. J. Med. Sci. 15, 1304–1311 (2018).
Yong, W. et al. The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1-NF-κB signaling axis. J. Exp. Clin. Cancer Res 38, 386 (2019).
Yong, W. et al. CD4+ T cells promote renal cell carcinoma proliferation via modulating YBX1. Exp. Cell Res. 363, 95–101 (2018).
Dong, W. et al. Activated protein C ameliorates renal ischemia-reperfusion injury by restricting Y-box binding protein-1 ubiquitination. J. Am. Soc. Nephrol. 26, 2789–2799 (2015).
Hanssen, L. et al. Y-box binding protein-1 mediates profibrotic effects of calcineurin inhibitors in the kidney. J. Immunol. 187, 298–308 (2011).
Gibbert, L. et al. YB-1 increases glomerular, but decreases interstitial fibrosis in CNI-induced nephropathy. Clin. Immunol. 194, 67–74 (2018).
Raffetseder, U. et al. Differential regulation of chemokine CCL5 expression in monocytes/macrophages and renal cells by Y-box protein-1. Kidney Int. 75, 185–196 (2009). This work provides important additional insight into the function of YBX1 in renal disease.
Hanssen, L. et al. YB-1 is an early and central mediator of bacterial and sterile inflammation in vivo. J. Immunol. 191, 2604–2613 (2013).
Bhreathnach, U. et al. Profibrotic IHG-1 complexes with renal disease associated HSPA5 and TRAP1 in mitochondria. Biochim. Biophys. Acta 1863, 896–906 (2017).
Wang, J. et al. Therapeutic nuclear shuttling of YB-1 reduces renal damage and fibrosis. Kidney Int. 90, 1226–1237 (2016). Important work as an example of how RBP function can be modulated to tackle renal disease.
Kato, M. et al. Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-β-induced collagen expression in kidney cells. J. Biol. Chem. 285, 3404–3415 (2010).
Van Roeyen, C. R. C. et al. Y-box protein 1 mediates PDGF-B effects in mesangioproliferative glomerular disease. J. Am. Soc. Nephrol. 16, 2985–2996 (2005). Central study regarding the RBP YBX1 in MPGN and its role in PDGFB signalling.
Webster, A. C., Nagler, E. V., Morton, R. L. & Masson, P. Chronic kidney disease. Lancet 389, 1238–1252 (2017).
Moranne, O. et al. Timing of onset of CKD-related metabolic complications. J. Am. Soc. Nephrol. 20, 164–171 (2009).
Bürki, R. et al. Impaired expression of key molecules of ammoniagenesis underlies renal acidosis in a rat model of chronic kidney disease. Nephrol. Dial. Transplant. 30, 770–781 (2015).
Mufti, J. et al. Role of AUF1 and HuR in the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in LLC-PK 1-F+ cells. Am. J. Physiol. Renal Physiol. 301, F1066–F1077 (2011).
Gummadi, L., Taylor, L. & Curthoys, N. P. Concurrent binding and modifications of AUF1 and HuR mediate the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in kidney cells. Am. J. Physiol. Renal Physiol. 303, F1545–F1554 (2012).
Muntner, P. et al. Hypertension awareness, treatment, and control in adults with CKD: results from the chronic renal insufficiency cohort (CRIC) study. Am. J. Kidney Dis. 55, 441–451 (2010).
Townsend, R. R. & Taler, S. J. Management of hypertension in chronic kidney disease. Nat. Rev. Nephrol. 11, 555–563 (2015).
Quinkler, M. et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation 112, 1435–1443 (2005).
Alexandrou, M. E. et al. Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials. J. Hypertens. 37, 2307–2324 (2019).
Viengchareun, S. et al. Osmotic stress regulates mineralocorticoid receptor expression in a novel aldosterone-sensitive cortical collecting duct cell line. Mol. Endocrinol. 23, 1948–1962 (2009).
Lema, I. et al. RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity. Cell. Mol. Life Sci. 74, 4587–4597 (2017).
Lema, I. et al. HuR-dependent editing of a new mineralocorticoid receptor splice variant reveals an osmoregulatory loop for sodium homeostasis. Sci. Rep. 7, 4835 (2017).
Viengchareun, S. et al. Hypertonicity compromises renal mineralocorticoid receptor signaling through Tis11b-mediated post-transcriptional control. J. Am. Soc. Nephrol. 25, 2213–2221 (2014). Important work regarding the role of an RBP in renal mineralocorticoid receptor signalling.
Igarashi, P. & Somlo, S. Polycystic kidney disease. J. Am. Soc. Nephrol. 18, 1371–1373 (2007).
Saffman, E. E. et al. Premature translation of oskar in oocytes lacking the RNA-binding protein bicaudal-C. Mol. Cell. Biol. 18, 4855–4862 (1998).
Gamberi, C. & Lasko, P. The Bic-C family of developmental translational regulators. Comp. Funct. Genomics 2012, 141386 (2012).
Zhang, Y. et al. Bicaudal-C spatially controls translation of vertebrate maternal mRNAs. RNA 19, 1575–1582 (2013).
Zhang, Y., Park, S., Blaser, S. & Sheets, M. D. Determinants of RNA binding and translational repression by the Bicaudal-C regulatory protein. J. Biol. Chem. 289, 7497–7504 (2014).
Dowdle, M. E. et al. A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development. Development 146, dev172486 (2019).
Lian, P. et al. Loss of polycystin-1 inhibits Bicc1 expression during mouse development. PLoS One 9, e88816 (2014).
Mohieldin, A. M. et al. Protein composition and movements of membrane swellings associated with primary cilia. Cell. Mol. Life Sci. 72, 2415–2429 (2015).
Cogswell, C. et al. Positional cloning of jcpk/bpk locus of the mouse. Mamm. Genome 14, 242–249 (2003).
Bouvrette, D. J., Price, S. J. & Bryda, E. C. K homology domains of the mouse polycystic kidney disease-related protein, Bicaudal-C (Bicc1), mediate RNA binding in vitro. Nephron Exp. Nephrol. 108, e27–e34 (2008).
Tran, U., Pickney, L. M., Özpolat, B. D. & Wessely, O. Xenopus Bicaudal-C is required for the differentiation of the amphibian pronephros. Dev. Biol. 307, 152–164 (2007).
Bouvrette, D. J., Sittaramane, V., Heidel, J. R., Chandrasekhar, A. & Bryda, E. C. Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease. Comp. Med. 60, 96–106 (2010).
Stagner, E. E., Bouvrette, D. J., Cheng, J. & Bryda, E. C. The polycystic kidney disease-related proteins Bicc1 and SamCystin interact. Biochem. Biophys. Res. Commun. 383, 16–21 (2009).
Bakey, Z. et al. The SAM domain of ANKS6 has different interacting partners and mutations can induce different cystic phenotypes. Kidney Int. 88, 299–310 (2015).
Brown, J. H. et al. Missense mutation in sterile α motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat. J. Am. Soc. Nephrol. 16, 3517–3526 (2005).
Rothé, B. et al. Crystal structure of Bicc1 SAM polymer and mapping of interactions between the ciliopathy-associated proteins Bicc1, ANKS3, and ANKS6. Structure 26, 209–224 (2018).
Fu, Y. et al. Loss of Bicc1 impairs tubulomorphogenesis of cultured IMCD cells by disrupting E-cadherin-based cell-cell adhesion. Eur. J. Cell Biol. 89, 428–436 (2010).
Maisonneuve, C. et al. Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow. Development 136, 3019–3030 (2009).
Kraus, M. R. C. et al. Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia. Hum. Mutat. 33, 86–90 (2012).
Piazzon, N., Maisonneuve, C., Guilleret, I., Rotman, S. & Constam, D. B. Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing. J. Mol. Cell Biol. 4, 398–408 (2012).
Tran, U. et al. The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development 137, 1107–1116 (2010). This work not only implicates the RBP bicaudal C in PKD but also shows its molecular function by antagonizing an miRNA known to play a role in cystogenesis.
Lemaire, L. A. et al. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis. Development 142, 858–870 (2015).
Leal-Esteban, L. C., Rothé, B., Fortier, S., Isenschmid, M. & Constam, D. B. Role of bicaudal C1 in renal gluconeogenesis and its novel interaction with the CTLH complex. PLoS Genet. 14, e1007487 (2018).
Gamberi, C., Hipfner, D. R., Trudel, M. & Lubell, W. D. Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila. PLoS Genet. 13, e1006694 (2017).
Debaize, L. & Troadec, M. B. The master regulator FUBP1: its emerging role in normal cell function and malignant development. Cell. Mol. Life Sci. 76, 259–281 (2019).
Zheng, W. et al. Far upstream element-binding protein 1 binds the 39 untranslated region of PKD2 and suppresses its translation. J. Am. Soc. Nephrol. 27, 2645–2657 (2016).
Liu, Y. Cellular and molecular mechanisms of renal fibrosis. Nat. Rev. Nephrol. 10, 493–503 (2011).
Meng, X. M., Nikolic-Paterson, D. J. & Lan, H. Y. Inflammatory processes in renal fibrosis. Nat. Rev. Nephrol. 10, 493–503 (2014).
Bülow, R. D. & Boor, P. Extracellular matrix in kidney fibrosis: more than just a scaffold. J. Histochem. Cytochem. 67, 643–661 (2019).
Gregorini, M. et al. Mesenchymal stromal cells prevent renal fibrosis in a rat model of unilateral ureteral obstruction by suppressing the renin-angiotensin system via HuR. PLoS One 11, e0148542 (2016).
Chen, X. et al. The potential role of retinoic acid receptor α on glomerulosclerosis in rats and podocytes injury is associated with the induction of MMP2 and MMP9. Acta Biochim. Biophys. Sin. 49, 669–679 (2017).
Tsai, J. P. et al. Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis. PLoS One 7, e48164 (2012).
Wang, X. et al. Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy. Am. J. Physiol. Renal Physiol. 299, F973–F982 (2010).
Yokoo, T. & Kitamura, M. Dual regulation of IL-1β-mediated matrix metalloproteinase-9 expression in mesangial cells by NF-kappaB and AP-1. Am. J. Physiol. 270, F123–F130 (1996).
Huwiler, A. et al. ATP potentiates interleukin-1β-induced MMP-9 expression in mesangial cells via recruitment of the ELAV Protein HuR. J. Biol. Chem. 278, 51758–51769 (2003). This study provides first evidence of the role of the RBP HuR in mesangial cells.
Akool, E.-S. et al. Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR. Mol. Cell. Biol. 23, 4901–4916 (2003).
Cok, S. J., Acton, S. J. & Morrison, A. R. The proximal region of the 3′-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U. J. Biol. Chem. 278, 36157–36162 (2003).
Doller, A. et al. Protein kinase Cα-dependent phosphorylation of the mRNA-stabilizing factor HuR: Implications for posttranscriptional regulation of cyclooxygenase-2. Mol. Biol. Cell 28, 2608–2625 (2007).
Doller, A. et al. Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cδ elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA. Mol. Cell. Biol. 28, 2608–2625 (2008).
Doller, A. et al. Angiotensin II induces renal plasminogen activator inhibitor-1 and cyclooxygenase-2 expression post-transcriptionally via activation of the mRNA-stabilizing factor human-antigen R. Am. J. Pathol. 174, 1252–1263 (2009).
Kitching, A. R. et al. Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis. J. Am. Soc. Nephrol. 14, 1487–1495 (2003).
Kurogi, Y. Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease. Med. Res. Rev. 23, 15–31 (2003).
Lang, S., Hartner, A., Sterzel, R. B. & Schöcklmann, H. O. Requirement of cyclin D1 in mesangial cell mitogenesis. J. Am. Soc. Nephrol. 11, 1398–1408 (2000).
Doller, A., Schlepckow, K., Schwalbe, H., Pfeilschifter, J. & Eberhardt, W. Tandem phosphorylation of serines 221 and 318 by protein kinase Cδ coordinates mRNA binding and nucleocytoplasmic shuttling of HuR. Mol. Cell. Biol. 30, 1397–1410 (2010).
Che, Y. et al. AngiotensinII induces HuR shuttling by post-transcriptional regulated cyclinD1 in human mesangial cells. Mol. Biol. Rep. 41, 1141–1150 (2014).
Lellek, H. et al. Purification and molecular cloning of a novel essential component of the apolipoprotein B mRNA editing enzyme-complex. J. Biol. Chem. 275, 19848–19856 (2000).
Snyder, E. M. et al. APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo. RNA 23, 457–465 (2017).
Huang, L. et al. Apobec-1 complementation factor (A1CF) inhibits epithelial-mesenchymal transition and migration of normal rat kidney proximal tubular epithelial cells. Int. J. Mol. Sci. 17, 197 (2016).
Kumar, R. Pin1 regulates parathyroid hormone mRNA stability. J. Clin. Invest. 119, 2887–2891 (2009).
Yan, J. et al. AUF1 modulates TGF-β signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression. Biochim. Biophys. Acta Mol. Cell Res. 1865, 48–56 (2018).
Gao, S. et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-β signaling. Mol. Cell 36, 457–468 (2009).
Stradiot, L., Mannaerts, I. & Van Grunsven, L. A. P311, friend, or foe of tissue fibrosis? Front. Pharmacol. 9, 1151 (2018).
Yue, M. M. et al. Novel RNA-binding protein P311 binds Eukaryotic translation initiation factor 3 subunit B (eIF3b) to promote translation of transforming growth factor β1-3 (TGF-β1-3). J. Biol. Chem. 289, 33971–33983 (2014).
Wang, F. et al. Expression of P311, a transforming growth factor beta latency-associated protein-binding protein, in human kidneys with IgA nephropathy. Int. Urol. Nephrol. 42, 811–819 (2010).
Zhang, Y. et al. Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells. Ren. Fail. 37, 1384–1389 (2015).
Yao, Z. et al. P311 promotes renal fibrosis via TGFβ1/Smad signaling. Sci. Rep. 5, 17032 (2015).
Wei, Z. et al. Molecular mechanism of mesenchyme homeobox 1 in transforming growth factor β1–induced P311 gene transcription in fibrosis. Front. Mol. Biosci. 7, 59 (2020).
Qi, F., Cai, P., Liu, X., Peng, M. & Si, G. Adenovirus-mediated P311 inhibits TGF-β1-induced epithelial–mesenchymal transition in NRK-52E cells via TGF-β1-Smad-ILK pathway. Biosci. Trends 9, 299–306 (2015).
Qi, F. H., Cai, P. P., Liu, X. & Si, G. M. Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats. Int. J. Mol. Med. 41, 3015–3023 (2018).
Wagener, N. et al. Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney. Br. J. Cancer 97, 1271–1276 (2007).
Zhou, J. & Jiang, H. Livin is involved in TGF-β1-induced renal tubular epithelial-mesenchymal transition through lncRNA-ATB. Ann. Transl. Med. 7, 463 (2019).
das Chagas, P. F., Baroni, M., Brassesco, M. S. & Tone, L. G. Interplay between the RNA binding-protein Musashi and developmental signaling pathways. J. Gene Med. 22, e3136 (2020).
Jadhav, S. et al. RNA-binding protein Musashi homologue 1 regulates kidney fibrosis by translational inhibition of p21 and Numb mRNA. J. Biol. Chem. 291, 14085–14094 (2016). Important work showing how an RBP (MSI1) impacts on renal fibrogenesis by binding to its target mRNAs.
Ume, A. C., Wenegieme, T.-Y. & Williams, C. R. Calcineurin inhibitors: a double-edged sword. Am. J. Physiol. Renal Physiol. 320, F336–F341 (2020).
Wang, J. et al. YB-1 orchestrates onset and resolution of renal inflammation via IL10 gene regulation. J. Cell. Mol. Med. 21, 3494–3505 (2017).
Bernhardt, A. et al. Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1. Kidney Int. 92, 1157–1177 (2017).
Ewert, L. et al. Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage. Atherosclerosis 278, 156–165 (2018).
Brandt, S. et al. Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients. Sci. Rep. 9, 19103 (2019).
Hermert, D. et al. The nucleic acid binding protein YB-1-controlled expression of CXCL-1 modulates kidney damage in liver fibrosis. Kidney Int. 97, 741–752 (2020).
Thomas, M. C. et al. Diabetic kidney disease. Nat. Rev. Dis. Prim. 1, 15018 (2015).
Navarro-González, J. F., Mora-Fernández, C., De Fuentes, M. M. & García-Pérez, J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat. Rev. Nephrol. 7, 327–340 (2011).
Yu, C. et al. Human antigen R mediated post-transcriptional regulation of epithelial-mesenchymal transition related genes in diabetic nephropathy. J. Diabetes 7, 562–572 (2015).
Li, X. et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Exp. Cell Res. 350, 327–335 (2017).
Shahzad, K. et al. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int. 87, 74–84 (2015).
Du, P. et al. NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy. Kidney Int. 84, 265–276 (2013).
Shang, J. et al. Identification of NOD2 as a novel target of RNA-binding protein HuR: evidence from NADPH oxidase-mediated HuR signaling in diabetic nephropathy. Free Radic. Biol. Med. 79, 217–227 (2015).
Shi, Q. et al. Interplay between RNA-binding protein HuR and Nox4 as a novel therapeutic target in diabetic kidney disease. Mol. Metab. 36, 100968 (2020).
Guo, J. et al. RNA-binding proteins tristetraprolin and human antigen R are novel modulators of podocyte injury in diabetic kidney disease. Cell Death Dis. 11, 413 (2020). This study shows the interactions between two RBPs regarding podocyte injury in diabetic kidney disease.
Brooks, S. A. & Blackshear, P. J. Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim. Biophys. Acta 1829, 666–679 (2013).
Taylor, G. A. et al. A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4, 445–454 (1996).
Liu, F. et al. The expression of tristetraprolin and its relationship with urinary proteins in patients with diabetic nephropathy. PLoS One 10, e0141471 (2015).
Guo, J. et al. MiRNA-29c regulates the expression of inflammatory cytokines in diabetic nephropathy by targeting tristetraprolin. Sci. Rep. 7, 2314 (2017).
Zhang, Q., Wu, G., Guo, S., Liu, Y. & Liu, Z. Effects of tristetraprolin on doxorubicin (adriamycin)-induced experimental kidney injury through inhibiting IL-13/STAT6 signal pathway. Am. J. Transl. Res. 12, 1203–1221 (2020).
Christiansen, J., Kolte, A. M., Hansen, T. V. O. & Nielsen, F. C. IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J. Mol. Endocrinol. 43, 187–195 (2009).
Gu, T. et al. IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy. J. Diabetes Complications 26, 393–398 (2012).
Schaeffer, V., Hansen, K. M., Morris, D. R., LeBoeuf, R. C. & Abrass, C. K. RNA-binding protein IGF2BP2/IMP2 is required for laminin-β2 mRNA translation and is modulated by glucose concentration. Am. J. Physiol. Renal Physiol. 303, F75–F82 (2012).
Jing, F., Zhao, J., Jing, X. & Lei, G. Long noncoding RNA Airn protects podocytes from diabetic nephropathy lesions via binding to Igf2bp2 and facilitating translation of Igf2 and Lamb2. Cell Biol. Int. 44, 1860–1869 (2020).
Jiang, X. et al. Metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway. Oxid. Med. Cell. Longev. 2020, 8708236 (2020).
Wiley, C. D. Role of senescent renal cells in pathophysiology of diabetic kidney disease. Curr. Diabetes Rep. 20, 1–7 (2020).
Du, Y. et al. Butyrate alleviates diabetic kidney disease by mediating the miR-7a-5p/P311/TGF-β1 pathway. FASEB J. 34, 10462–10475 (2020).
Christodoulou-Vafeiadou, E. et al. Divergent innate and epithelial functions of the RNA-binding protein HuR in intestinal inflammation. Front. Immunol. 9, 2732 (2018).
Nyati, K. K., Zaman, M. M.-U., Sharma, P. & Kishimoto, T. Arid5a, an RNA-binding protein in immune regulation: RNA stability, inflammation, and autoimmunity. Trends Immunol. 41, 255–268 (2020).
Chelsey, J. L. et al. Reduction of the RNA binding protein TIA1 exacerbates neuroinflammation in tauopathy. Front. Neurosci. 14, 285 (2020).
Emine, S., Suna Özbaş, T. & Jülide, A. Inhibition of glomerular mesangial cell proliferation by siPDGF-B- and siPDGFR-β-containing chitosan nanoplexes. AAPS PharmSciTech 18, 1031–1042 (2017).
Jürgen, F., Frank, E. & Charles, E. A. A new look at platelet-derived growth factor in renal disease. J. Am. Soc. Nephrol. 19, 12–23 (2008).
Raffetseder, U. et al. Extracellular YB-1 blockade in experimental nephritis upregulates Notch-3 receptor expression and signaling. Nephron Exp. Nephrol. 118, e100–e108 (2011).
Zhu, X. et al. Protein phosphatase 2A modulates podocyte maturation and glomerular functional integrity in mice. Cell Commun. Signal. 17, 91 (2019).
Liu, S. et al. Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis. Clin. Sci. 134, 1433–1448 (2020).
Das, S. & Krainer, A. R. Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol. Cancer Res. 12, 1195–1204 (2014).
Kono, M. et al. Decreased expression of serine/arginine-rich splicing factor 1 in T cells from patients with active systemic lupus erythematosus accounts for reduced expression of RasGRP1 and DNA methyltransferase 1. Arthritis Rheumatol. 70, 2046–2056 (2018).
Katsuyama, T., Li, H., Comte, D., Tsokos, G. C. & Moulton, V. R. Splicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity. J. Clin. Invest. 129, 5411–5423 (2019). Important work showing the impact of the SLE-associated RBP SRSF1 in nephrotoxic serum nephritis.
Katsuyama, T., Li, H., Krishfield, S. M., Kyttaris, V. C. & Moulton, V. R. Splicing factor SRSF1 limits IFN-γ production via RhoH and ameliorates experimental nephritis. Rheumatology 60, 420–429 (2020).
Wu, P. Inhibition of RNA-binding proteins with small molecules. Nat. Rev. Chem. 4, 441–458 (2020).
Lieberman, J. Tapping the RNA world for therapeutics. Nat. Struct. Mol. Biol. 25, 357–364 (2018).
Mohibi, S., Chen, X. & Zhang, J. Cancer the ‘RBP’ eutics–RNA-binding proteins as therapeutic targets for cancer. Pharmacol. Ther. 203, 107390 (2019).
Sanna, M. D., Quattrone, A. & Galeotti, N. Silencing of the RNA-binding protein HuR attenuates hyperalgesia and motor disability in experimental autoimmune encephalomyelitis. Neuropharmacology 123, 116–125 (2017).
Fox, R. G. et al. Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma. Nature 534, 407–411 (2016).
Amreddy, N. et al. Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment. Nanomed. Nanotechnol. Biol. Med. 14, 373–384 (2018).
Huang, Y. H. et al. Delivery of therapeutics targeting the mRNA binding protein HuR Using 3DNA nanocarriers suppresses ovarian tumor growth. Cancer Res. 76, 1549–1559 (2016).
Chen, H. et al. Inhibition of RNA-binding protein Musashi-1 suppresses malignant properties and reverses paclitaxel resistance in ovarian carcinoma. J. Cancer 10, 1580–1592 (2019).
Baranello, G. et al. Risdiplam in type 1 spinal muscular atrophy. N. Engl. J. Med. 384, 915–923 (2021).
Adams, D. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379, 11–21 (2018).
Balwani, M. et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N. Engl. J. Med. 382, 2289–2301 (2020).
Agency, E. M. First treatment for rare condition primary hyperoxaluria type 1. https://www.ema.europa.eu/en/news/first-treatment-rare-condition-primary-hyperoxaluria-type-1 (2020).
Dammes, N. & Peer, D. Paving the road for RNA therapeutics. Trends Pharmacol. Sci. 41, 755–775 (2020).
Meisner, N. C. et al. Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR. Nat. Chem. Biol. 3, 508–515 (2007).
Blanco, F. F. et al. Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis. Oncotarget 7, 74043–74058 (2016).
Lang, M. et al. HuR small-molecule inhibitor elicits differential effects in adenomatosis polyposis and colorectal carcinogenesis. Cancer Res. 77, 2424–2438 (2017).
Muralidharan, R. et al. HuR-targeted small molecule inhibitor exhibits cytotoxicity towards human lung cancer cells. Sci. Rep. 7, 9694 (2017).
Allegri, L. et al. The HuR CMLD-2 inhibitor exhibits antitumor effects via MAD2 downregulation in thyroid cancer cells. Sci. Rep. 9, 7374 (2019).
Lan, L. et al. Natural product derivative Gossypolone inhibits Musashi family of RNA-binding proteins. BMC Cancer 18, 809 (2018).
Clingman, C. C. et al. Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite. eLife 14, e02848 (2014).
Law, J. H. et al. Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability. PLoS One 5, 1–11 (2010).
Sechi, M. et al. Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models. Sci. Rep. 8, 15726 (2018).
Tiwari, A. et al. Blocking y-box binding protein-1 through simultaneous targeting of PI3K and MAPK in triple negative breast cancers. Cancers 12, 1–19 (2020).
Hasegawa, M. et al. A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosis. Arthritis Rheum. 60, 3465–3475 (2009).
Ding, S., Xu, Y., Hao, T. & Ma, P. Partial least squares based gene expression analysis in renal failure. Diagn. Pathol. 9, 137 (2014).
Täuber, H., Hüttelmaier, S. & Köhn, M. POLIII-derived non-coding RNAs acting as scaffolds and decoys. J. Mol. Cell Biol. 11, 880–885 (2019).
Liepelt, A. et al. Identification of RNA-binding proteins in macrophages by interactome capture. Mol. Cell. Proteom. 15, 2699–2714 (2016).
Perez-Perri, J. I. et al. Discovery of RNA-binding proteins and characterization of their dynamic responses by enhanced RNA interactome capture. Nat. Commun. 9, 4408 (2018). This work represents an important addition to the current toolbox for RNA-interactome capture (RIC) using LNA-modified probes and allowing for RIC from tissue.
Trendel, J. et al. The human RNA-binding proteome and its dynamics during translational arrest. Cell 176, 391–403.e19 (2019). One of the three key publications implementing organic phase extraction as a central technique exploiting the unique biophysical properties of crosslinked RNA-protein complexes to enrich and isolate RNPs.
Backlund, M. et al. Plasticity of nuclear and cytoplasmic stress responses of RNA-binding proteins. Nucleic Acids Res. 48, 4725–4740 (2020).
Perez-Perri, J. I. et al. Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture. Nat. Protoc. 16, 27–60 (2021).
Liao, Y. et al. The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease. Cell Rep. 16, 1456–1469 (2016).
Castello, A. et al. Comprehensive identification of RNA-binding domains in human cells. Mol. Cell 63, 696–710 (2016). Key study establishing a technique to identify RNA-binding domains in global RPBomes by partial tryptic digest.
Urdaneta, E. C. et al. Purification of cross-linked RNA-protein complexes by phenol-toluol extraction. Nat. Commun. 10, 990 (2019). One of the three key publications implementing organic phase extraction as a central technique exploiting the unique biophysical properties of crosslinked RNA-protein complexes to enrich and isolate RNPs.
Queiroz, R. M. L. et al. Comprehensive identification of RNA–protein interactions in any organism using orthogonal organic phase separation (OOPS). Nat. Biotechnol. 37, 169–178 (2019). One of the three key publications implementing organic phase extraction as a central technique exploiting the unique biophysical properties of crosslinked RNA-protein complexes to enrich and isolate RNPs.
R.-U.M. has received honoraria for counselling and participation in advisory boards from Alnylam Pharmaceuticals. The other authors declare no competing interests.
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- MiRNA sponges
Transcripts (for example, circRNAs) that contain multiple complementary sites that bind and sequester specific miRNAs to prevent them from interacting with their target RNAs.
- Protein sponges
Transcripts (for example, circRNAs) that sequester proteins to withdraw them from the cellular pool and thereby influence their cellular functions.
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Seufert, L., Benzing, T., Ignarski, M. et al. RNA-binding proteins and their role in kidney disease. Nat Rev Nephrol 18, 153–170 (2022). https://doi.org/10.1038/s41581-021-00497-1