Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Heat stress induced arginylation of HuR promotes alternative polyadenylation of Hsp70.3 by regulating HuR stability and RNA binding

Abstract

Arginylation was previously found to promote stabilization of heat shock protein 70.3 (Hsp70.3) mRNA and cell survival in mouse embryonic fibroblasts (MEFs) on exposure to heat stress (HS). In search of a factor responsible for these phenomena, the current study identified human antigen R (HuR) as a direct target of arginylation. HS induced arginylation of HuR affected its stability and RNA binding activity. Arginylated HuR failed to bind Hsp70.3 3′ UTR, allowing the recruitment of cleavage stimulating factor 64 (CstF64) in the proximal poly-A-site (PAS), generating transcripts with short 3′UTR. However, HuR from Ate1 knock out (KO) MEFs bound to proximal PAS region with higher affinity, thus excluded CstF64 recruitment. This inhibited the alternative polyadenylation (APA) of Hsp70.3 mRNA and generated the unstable transcripts with long 3′UTR. The inhibition of RNA binding activity of HuR was traced to arginylation-coupled phosphorylation of HuR, by check point kinase 2 (Chk2). Arginylation of HuR occurred at the residue D15 and the arginylation was needed for the phosphorylation. Accumulation of HuR also decreased cell viability upon HS. In conclusion, arginylation dependent modifications of HuR maintained its cellular homeostasis, and promoted APA of Hsp70.3 pre-mRNA, during early HS response.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Loss of arginylation inhibits alternative polyadenylation of Hsp70.3 pre mRNA upon HS.
Fig. 2: Arginylation promotes proteasomal degradation of HuR and enhances cell survival upon HS.
Fig. 3: Arginylation regulated differential binding of HuR and CstF64 to Hsp70.3 3′UTR.
Fig. 4: Arginylation regulates CHK2 dependent phosphorylation of HuR which alters its binding to Hsp70.3 3’UTR.
Fig. 5: HuR acts as a direct target of arginylation and undergoes high molecular weight modification upon HS.
Fig. 6: Arginylation of HuR at position D15 acts as a pre-requisite factor for its phosphorylation which in turn regulates its RNA binding activity and APA of Hsp70.3.

References

  1. 1.

    Bachmair A, Finley D, Varshavsky A. In vivo half-life of a protein is a function of its amino-terminal residue. Science. 1986;234:179–86.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Ferber S, Ciechanover A. Role of arginine-tRNA in protein degradation by the ubiquitin pathway. Nature. 1987;326:808.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Kaji H, Kaji A. Protein modification by arginylation. Chem Biol. 2011;18:6–7.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Kaji H. Amino-terminal arginylation of chromosomal proteins by arginyl-tRNA. Biochemistry. 1976;15:5121–5.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Wong CC, Xu T, Rai R, Bailey AO, Yates 3rdJR, Wolf YI, et al. Global analysis of posttranslational protein arginylation. PLoS Biol. 2007;5:e258.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Wang J, Han X, Wong CC, Cheng H, Aslanian A, Xu T, et al. Arginyltransferase ATE1 catalyzes midchain arginylation of proteins at side chain carboxylates in vivo. Chem Biol. 2014;21:331–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Eriste E, Norberg Å, Nepomuceno D, Kuei C, Kamme F, Tran D-T, et al. A novel form of neurotensin post-translationally modified by arginylation. J Biol Chem. 2005;280:35089–97.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Wang J, Pejaver VR, Dann GP, Wolf MY, Kellis M, Huang Y, et al. Target site specificity and in vivo complexity of the mammalian arginylome. Sci Rep. 2018;8:16177.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  9. 9.

    Wang J, Han X, Leu NA, Sterling S, Kurosaka S, Fina M, et al. Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration. Sci Rep. 2017;7:1–14.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Elias S, Ciechanover A. Post-translational addition of an arginine moiety to acidic NH2 termini of proteins is required for their recognition by ubiquitin-protein ligase. J Biol Chem. 1990;265:15511–7.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Karakozova M, Kozak M, Wong CC, Bailey AO, Yates JR, Mogilner A, et al. Arginylation of ß-actin regulates actin cytoskeleton and cell motility. Science. 2006;313:192–6.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Saha S, Mundia MM, Zhang F, Demers RW, Korobova F, Svitkina T, et al. Arginylation regulates intracellular actin polymer level by modulating actin properties and binding of capping and severing proteins. Mol Biol Cell. 2010;21:1350–61.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Zhang F, Patel DM, Colavita K, Rodionova I, Buckley B, Scott DA, et al. Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase. Nat Commun. 2015;6:7517.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Piatkov KI, Brower CS, Varshavsky A. The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments. Proc Natl Acad Sci. 2012;109:E1839–47.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Rai R, Zhang F, Colavita K, Leu NA, Kurosaka S, Kumar A, et al. Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers. Oncogene. 2016;35:4058.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Singh A, Borah AK, Deka K, Gogoi AP, Verma K, Barah P, et al. Arginylation regulates adipogenesis by regulating expression of PPARγ at transcript and protein level. Biochim Biophys Acta. 2019;1864:596–607.

    CAS  Article  Google Scholar 

  17. 17.

    Davydov IV, Varshavsky AJJoBC. RGS4 is arginylated and degraded by the N-end rule pathway in vitro. J Biol Chem. 2000;275:22931–41.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Cha-Molstad H, Sung KS, Hwang J, Kim KA, Yu JE, Yoo YD, et al. Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat Cell Biol. 2015;17:917.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Decca MB, Carpio MA, Bosc C, Galiano MR, Job D, Andrieux A, et al. Post-translational arginylation of calreticulin: a new isospecies of calreticulin component of stress granules. J Biol Chem. 2007;282:8237–45.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, et al. RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. Proc Natl Acad Sci. 2005;102:15030–5.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    White MD, Klecker M, Hopkinson RJ, Weits DA, Mueller C, Naumann C, et al. Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets. Nat Commun. 2017;8:14690.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Carpio MA, Decca MB, Sambrooks CL, Durand ES, Montich GG, Hallak ME. Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding. Int J Biochem Cell Biol. 2013;45:1223–35.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Zhang F, Saha S, Kashina A. Arginylation-dependent regulation of a proteolytic product of talin is essential for cell–cell adhesion. J Cell Biol. 2012;197:819–36.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Saha S, Kashina A. Posttranslational arginylation as a global biological regulator. Dev Biol. 2011;358:1–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Hu R-G, Sheng J, Qi X, Xu Z, Takahashi TT, Varshavsky A. The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators. Nature. 2005;437:981.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Lamon KD, Kaji H. Arginyl-tRNA transferase activity as a maker of cellular aging in peripheral rat tissues. Exp Gerontol. 1980;15:53–64.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Deka K, Singh A, Chakraborty S, Mukhopadhyay R, Saha S. Protein arginylation regulates cellular stress response by stabilizing HSP70 and HSP40 transcripts. Cell Death Discov. 2016;2:16074.

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Deka K, Saha S. Arginylation: a new regulator of mRNA stability and heat stress response. Cell Death Dis. 2017;8:e2604.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Banerji S, Berg L, Morimoto RI. Transcription and post-transcriptional regulation of avian HSP70 gene expression. J Biol Chem. 1986;261:15740–5.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Morimoto RI, Kroeger P, Cotto J. The transcriptional regulation of heat shock genes: a plethora of heat shock factors and regulatory conditions. In: Stress-inducible cellular responses. (Eds. Feige U, Yahara I, Morimoto RI, Polla BS) New York: Springer; 1996. p. 139–63.

  31. 31.

    Morimoto RI. Cells in stress: transcriptional activation of heat shock genes. Science. 1993;259:1409–1409.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Theodorakis NG, Morimoto RI. Posttranscriptional regulation of hsp70 expression in human cells: effects of heat shock, inhibition of protein synthesis, and adenovirus infection on translation and mRNA stability. Mol Cell Biol. 1987;7:4357–68.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Kwon YT, Kashina AS, Davydov IV, Hu R-G, An JY, Seo JW, et al. An essential role of N-terminal arginylation in cardiovascular development. Science. 2002;297:96–99.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Mayr C, Bartel DP. Widespread shortening of 3′ UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 2009;138:673–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Arienti KL, Brunmark A, Axe FU, McClure K, Lee A, Blevitt J, et al. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med. Chem. 2005;48:1873–85.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Dai B, Zhao XF, Mazan-Mamczarz K, Hagner P, Corl S, Bahassi EM, et al. Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma. Nat Commun. 2011;2:1–9.

    Google Scholar 

  37. 37.

    Thakuri PS, Gupta M, Singh S, Joshi R, Glasgow E, Lekan A, et al. Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling. BMC Cancer. 2020;20:1–14.

    Article  CAS  Google Scholar 

  38. 38.

    Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010;5:725.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Yang J, Zhang Y. I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Res. 2015;43:W174–81.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinform. 2008;9:40.

    Article  CAS  Google Scholar 

  41. 41.

    Hinman M, Lou H. Diverse molecular functions of Hu proteins. Cell Mol Life Sci. 2008;65:3168.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25:1605–12.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    de Lorenzo L, Sorenson R, Bailey-Serres J, Hunt AG. Noncanonical alternative polyadenylation contributes to gene regulation in response to hypoxia. Plant Cell. 2017;29:1262–77.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC, et al. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci. 2007;104:6758–63.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Hollerer I, Curk T, Haase B, Benes V, Hauer C, Neu-Yilik G, et al. The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion. RNA. 2016;22:1441–53.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Liu Y, Hu W, Murakawa Y, Yin J, Wang G, Landthaler M, et al. Cold-induced RNA-binding proteins regulate circadian gene expression by controlling alternative polyadenylation. Sci Rep. 2013;3:2054.

    PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Zheng D, Wang R, Ding Q, Wang T, Xie B, Wei L, et al. Cellular stress alters 3′ UTR landscape through alternative polyadenylation and isoform-specific degradation. Nat Commun. 2018;9:2268.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 48.

    Tranter M, Helsley RN, Paulding WR, McGuinness M, Brokamp C, Haar L, et al. Coordinated post-transcriptional regulation of Hsp70. 3 gene expression by microRNA and alternative polyadenylation. J Biol Chem. 2011;286:29828–37.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Kraynik SM, Gabanic A, Anthony SR, Kelley M, Paulding WR, Roessler A, et al. The stress-induced heat shock protein 70.3 expression is regulated by a dual-component mechanism involving alternative polyadenylation and HuR. Biochim Biophys Acta. 2015;1849:688–96.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Abdelmohsen K, Srikantan S, Yang X, Lal A, Kim HH, Kuwano Y, et al. Ubiquitin‐mediated proteolysis of HuR by heat shock. EMBO J. 2009;28:1271–82.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Dai W, Zhang G, Makeyev EV. RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage. Nucleic Acids Res. 2011;40:787–800.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 52.

    Dickson AM, Anderson JR, Barnhart MD, Sokoloski KJ, Oko L, Opyrchal M, et al. Dephosphorylation of HuR protein during alphavirus infection is associated with HuR relocalization to the cytoplasm. J Biol Chem. 2012;287:36229–38.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Grammatikakis I, Abdelmohsen K, Gorospe M. Posttranslational control of HuR function. Wiley Interdiscip Rev. 2017;8:e1372.

    Article  CAS  Google Scholar 

  54. 54.

    Abdelmohsen K, Pullmann JrR, Lal A, Kim HH, Galban S, Yang X, et al. Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Mol Cell. 2007;25:543–57.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Masuda K, Abdelmohsen K, Kim MM, Srikantan S, Lee EK, Tominaga K, et al. Global dissociation of HuR–mRNA complexes promotes cell survival after ionizing radiation. EMBO J. 2011;30:1040–53.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Fan XC, STEITZ JA. Overexpression of HuR, a nuclear–cytoplasmic shuttling protein, increases the in vivo stability of ARE‐containing mRNAs. EMBO J. 1998;17:3448–60.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Saha S, Wang J, Buckley B, Wang Q, Lilly B, Chernov M, et al. Small molecule inhibitors of arginyltransferase regulate arginylation-dependent protein degradation, cell motility, and angiogenesis. Biochem Pharmacol. 2012;83:866–73.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Kaur P, Hurwitz MD, Krishnan S, Asea A. Combined hyperthermia and radiotherapy for the treatment of cancer. Cancers. 2011;3:3799–823.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Murphy ME. The HSP70 family and cancer. Carcinogenesis. 2013;34:1181–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. 60.

    Tranter M, Ren X, Forde T, Wilhide ME, Chen J, Sartor MA, et al. NF-κB driven cardioprotective gene programs; Hsp70. 3 and cardioprotection after late ischemic preconditioning. J Mol Cell Cardiol. 2010;49:664–72.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    Turturici G, Sconzo G, Geraci F. Hsp70 and its molecular role in nervous system diseases. Biochem Res Int. 2011;2011.

  62. 62.

    Wu G, Osada M, Guo Z, Fomenkov A, Begum S, Zhao M, et al. ΔNp63α up-regulates the Hsp70 gene in human cancer. Cancer Res. 2005;65:758–66.

    CAS  PubMed  Google Scholar 

  63. 63.

    Peng SSY, Chen CYA, Xu N, Shyu AB. RNA stabilization by the AU‐rich element binding protein, HuR, an ELAV protein. EMBO J. 1998;17:3461–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Brennan C, Steitz J. HuR and mRNA stability. Cell Mol life Sci. 2001;58:266–77.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Güttinger S, Mühlhäusser P, Koller-Eichhorn R, Brennecke J, Kutay U. Transportin2 functions as importin and mediates nuclear import of HuR. Proc Natl Acad Sci. 2004;101:2918–23.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    REBANE A, AAB A, STEITZ JA. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. RNA. 2004;10:590–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Gallouzi I-E, Steitz JA. Delineation of mRNA export pathways by the use of cell-permeable peptides. Science. 2001;294:1895–901.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Wang Z, Kiledjian M. The poly (A)-binding protein and an mRNA stability protein jointly regulate an endoribonuclease activity. Mol Cell Biol. 2000;20:6334–41.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Tran H, Maurer F, Nagamine Y. Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2. Mol Cell Biol. 2003;23:7177–88.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Wang W, Furneaux H, Cheng H, Caldwell MC, Hutter D, Liu Y, et al. HuR regulates p21 mRNA stabilization by UV light. Mol Cell Biol. 2000;20:760–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Gallouzi I-E, Brennan CM, Stenberg MG, Swanson MS, Eversole A, Maizels N, et al. HuR binding to cytoplasmic mRNA is perturbed by heat shock. Proc Natl Acad Sci. 2000;97:3073–8.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    GALLOUZI I-E, BRENNAN CM, STEITZ JA. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA. 2001;7:1348–61.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Tian B, Manley JL. Alternative polyadenylation of mRNA precursors. Nat Rev Mol Cell Biol. 2017;18:18.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Fesler A, Xu X, Zheng X, Li X, Jiang J, Russo JJ, et al. Identification of miR-215 mediated targets/pathways via translational immunoprecipitation expression analysis (TrIP-chip). Oncotarget. 2015;6:24463.

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Sabirzhanov B, Stoica B, Zhao Z, Loane D, Wu J, Dorsey S, et al. miR-711 upregulation induces neuronal cell death after traumatic brain injury. Cell Death Differ. 2016;23:654.

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Place RF, Noonan EJ. Non-coding RNAs turn up the heat: an emerging layer of novel regulators in the mammalian heat shock response. Cell Stress Chaperones. 2014;19:159–72.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Tang Q, Yuan Q, Li H, Wang W, Xie G, Zhu K, et al. miR-223/Hsp70/JNK/JUN/miR-223 feedback loop modulates the chemoresistance of osteosarcoma to cisplatin. Biochem Biophys Res Commun. 2018;497:827–34.

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Shehata RH, Abdelmoneim SS, Osman OA, Hasanain AF, Osama A, Abdelmoneim SS, et al. Deregulation of miR-34a and its chaperon Hsp70 in hepatitis C virus-induced liver cirrhosis and hepatocellular carcinoma patients. Asia Pac J Cancer Prev. 2017;18:2395.

    Google Scholar 

  79. 79.

    Moraes KC, Wilusz CJ, Wilusz J. CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA. 2006;12:1084–91.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. 80.

    Ueno S, Sagata N. Requirement for both EDEN and AUUUA motifs in translational arrest of Mos mRNA upon fertilization of Xenopus eggs. Dev Biol. 2002;250:156–67.

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

We thank Dr Anna Kashina (University of Pennsylvania, USA) for the WT and KO MEFs, ATE1 antibody. pMSCV-PIG was kindly provided by Dr David Bartel (MIT, USA). We thank Dr. A. N. Jha and Ms Sapna M. Borah, TU for their help with structure analysis; Dr. Gaurangi Maitra for careful editing of the text. SS is supported by SERB-India (EEQ/2016/000772 and EMR/2016/004001). KD is supported by scholarship from SERB-India (EEQ/2016/000772). We thank funding agencies for their support to MBBT, TU (UGC-SAP, DST FIST, DBT Strengthening, DBT-Hub, and DBT-BIF) and Department of Biotechnology, NIT, Durgapur (DST-FIST).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sougata Saha.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Edited by A. Degterev

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Deka, K., Saha, S. Heat stress induced arginylation of HuR promotes alternative polyadenylation of Hsp70.3 by regulating HuR stability and RNA binding. Cell Death Differ 28, 730–747 (2021). https://doi.org/10.1038/s41418-020-00619-5

Download citation

Search

Quick links