RNA-binding proteins articles within Nature Communications

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  • Article
    | Open Access

    Overexpression of human antigen R (HuR) correlates with high grade tumours and poor patient prognosis. Here, the authors engineer a TRIM21 biological PROTAC to demonstrate the benefit of a targeted protein degradation approach to deplete HuR, resulting in tumour growth inhibition in pre-clinical cancer models by altering the HuR-regulated proteome.

    • Alice Fletcher
    • , Dean Clift
    •  & James Hunt

  • Article
    | Open Access

    Predicting dynamic RNA-RBP interactions in diverse cell lines is an important challenge in unravelling RNA function and post-transcriptional regulatory mechanisms. Here, authors develop HDRNet, an end-to-end deep-learning-based framework for accurately predicting dynamic RBP binding events across various cellular conditions.

    • Haoran Zhu
    • , Yuning Yang
    •  & Xiangtao Li

  • Article
    | Open Access

    The identification of RNA-bound proteomes is hampered by a lack of quantitative metrics for evaluating RNA binding function. Here, the authors report LEAP-RBP as a method for purification of RNA-bound proteins and introduce signal-based metrics for robust profiling of RNA-bound proteomes.

    • JohnCarlo Kristofich
    •  & Christopher V. Nicchitta

  • Article
    | Open Access

    RNA-Binding Proteins (RBPs) are critical regulators of RNA biology. Here, the authors describe the Brain-pCLAP methodology, uncover the RBP atlas of the mouse brain and demonstrate the differential binding of the splicing factor RBM5 to Huntington’s disease relevant transcripts in R6/2 mice.

    • Meeli Mullari
    • , Nicolas Fossat
    •  & Michael L. Nielsen

  • Article
    | Open Access

    SARS-CoV-2 genome turnover is mediated by its N protein, but precise parameters driving the necessary RNA specificity have remained enigmatic. Here, Korn et al. reveal N’s N-terminal domain to distinguish regulatory viral RNA motifs with a preference for transiently folded elements of functional impact.

    • Sophie Marianne Korn
    • , Karthikeyan Dhamotharan
    •  & Andreas Schlundt

  • Article
    | Open Access

    Characterization of RNA-binding proteins (RBPs) in tissues has been hampered by technical constraints. Here, the authors describe ex vivo eRIC, a method for global profiling of RBPs active in mammalian organs, and report comprehensive RBP atlases from mouse brain, kidney and liver.

    • Joel I. Perez-Perri
    • , Dunja Ferring-Appel
    •  & Matthias W. Hentze

  • Article
    | Open Access

    The authors report an unusual mode of AU-rich RNA recognition by the RNA recognition motifs of DND1, a protein essential for germline development, in a 27.5 kDa NMR structure and provide additional insight on DND1 function from cell-based experiments.

    • Malgorzata M. Duszczyk
    • , Harry Wischnewski
    •  & Frédéric H.-T. Allain

  • Article
    | Open Access

    Here, the authors generated an artificial RNA molecule, or aptamer, specific for the Amyotrophic Lateral Sclerosis protein TDP-43. By interacting avidly with its target, the aptamer can be exploited to track TDP-43 phase transition in vitro and in cells.

    • Elsa Zacco
    • , Owen Kantelberg
    •  & Gian Gaetano Tartaglia

  • Article
    | Open Access

    RNA granules are important regulators of RNA metabolism. Here the authors report that RNA granules containing RNA helicase DDX6 disassemble during neuronal maturation.

    • Karl E. Bauer
    • , Niklas Bargenda
    •  & Michael A. Kiebler

  • Article
    | Open Access

    Many viral proteins are thought to be unlikely candidates for drug discovery as they lack obvious drug binding sites. Here, the authors use computational approaches followed by experimental validation to identify a cryptic pocket within the Ebola virus protein VP35.

    • Matthew A. Cruz
    • , Thomas E. Frederick
    •  & Gregory R. Bowman

  • Article
    | Open Access

    RNA-protein interactions play critical roles in post-transcriptional gene regulation. Here the authors demonstrate pRBS-ID, an updated MS/MS-based method that combines the benefits of photoactivatable ribonucleosides and the chemical cleavage of RNA.

    • Jong Woo Bae
    • , Sangtae Kim
    •  & Jong-Seo Kim

  • Article
    | Open Access

    Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.

    • Samoil Sekulovski
    • , Pascal Devant
    •  & Simon Trowitzsch

  • Article
    | Open Access

    New approaches to plant disease control are important for pathogens that are difficult to control by existing methods. Here, the authors report a potential strategy to combat plant viruses by cytosolic expressed protein-only RNase P and show its ability for in vitro cleavage of tRNA-like structures existing in many plant viruses.

    • Anthony Gobert
    • , Yifat Quan
    •  & Philippe Giegé

  • Article
    | Open Access

    In fission yeast, the antagonistic RNA-binding proteins Mmi1 and Mei2 respectively promote and inhibit meiotic mRNA degradation during mitotic growth. Here the authors show that the lncRNA mamRNA scaffolds Mmi1 and Mei2 proteins to enable their mutual controls.

    • Vedrana Andric
    • , Alicia Nevers
    •  & Mathieu Rougemaille

  • Article
    | Open Access

    The HIV-1 RNA-binding protein rev facilitates nuclear export of viral RNA. Here, the authors use native mass spectrometry to study the interactions between rev-derived peptides and rev response elements of HIV-1 RNA, providing mechanistic insights into rev recognition and recruitment.

    • Eva-Maria Schneeberger
    • , Matthias Halper
    •  & Kathrin Breuker

  • Article
    | Open Access

    So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.

    • Pravin Kumar Ankush Jagtap
    • , Tomáš Kubelka
    •  & Michael Sattler

  • Article
    | Open Access

    Human ADAR proteins are responsible for RNA editing, conversion of adenosine to inosine in double-stranded RNA. Here the authors report a previously unknown zinc ion-binding site in the catalytic domain of human ADAR1 using high throughput mutagenesis, biochemical assay and Rosetta-based protein structure modeling.

    • SeHee Park
    • , Erin E. Doherty
    •  & Peter A. Beal

  • Article
    | Open Access

    hnRNPA2 is involved in RNA metabolism and can form both functional amyloid-like fibrils in membraneless organelles, and pathogenic fibrils in neurodegenerative conditions. Here, the authors present the cryo-EM fibril structure of the wild-type hnRNPA2 low-complexity domain (LCD) and the crystal structure of a LCD segment with the disease causing D290V variant and discuss how mutations can transform fibril structure from a functional to a pathogenic form.

    • Jiahui Lu
    • , Qin Cao
    •  & David S. Eisenberg

  • Article
    | Open Access

    RNA G-quadruplexes (RG4s) have been functionally linked to cancer gene expression. Here, Herviou, Le Bras et al. have identified the protein machinery modulating RG4s and reveal the role and mechanism of hnRNP H/F and DHX36 in RG4-mediated translational regulation affecting cancer treatment in glioblastoma.

    • Pauline Herviou
    • , Morgane Le Bras
    •  & Stefania Millevoi

  • Article
    | Open Access

    Some transcription factors have been proposed to functionally interact with RNA to facilitate proper regulation of gene expression. Here the authors demonstrate that human Sox2 interact directly and with high affinity to RNAs through its HMG DNA-binding domain.

    • Zachariah E. Holmes
    • , Desmond J. Hamilton
    •  & Robert T. Batey

  • Article
    | Open Access

    The Staufen proteins recognize secondary structures in 3’-untranslated regions in mRNA transcripts and induce degradation of these mRNAs with the help of the RNA helicase UPF1. Here the authors report that the nonsense-mediated mRNA decay factor UPF2 mediates the interaction between Stau1 and UPF1 in Staufen-mediated mRNA decay.

    • Manjeera Gowravaram
    • , Juliane Schwarz
    •  & Sutapa Chakrabarti

  • Article
    | Open Access

    Processing bodies (P-bodies) are non-membrane-bound protein/RNA granules in the cytosol. Here the authors combine bioinformatics, NMR and cell based assays and find that lysine is enriched in the disordered regions of P-body-associated proteins and show that lysine-rich polypeptides form highly dynamic lysine/RNA-coacervates and lysine acetylation reverses liquid-liquid phase separation.

    • Tina Ukmar-Godec
    • , Saskia Hutten
    •  & Markus Zweckstetter

  • Article
    | Open Access

    Comprehensive characterisation of RNA-protein interactions requires different levels of resolution. Here, the authors present an integrated mass spectrometry-based approach that allows them to define the Drosophila RNA-protein interactome from the level of multisubunit complexes down to the RNA-binding amino acid.

    • Amol Panhale
    • , Florian M. Richter
    •  & Asifa Akhtar

  • Article
    | Open Access

    RNA binding proteins are important regulators of RNA function. Here the authors describe a method for isolation of RNA-protein complexes that does not rely on a specific RNA sequence or motif, and demonstrate the approach by providing the global RNA-bound proteomes of human HEK293 cells and Salmonella Typhimurium.

    • Erika C. Urdaneta
    • , Carlos H. Vieira-Vieira
    •  & Benedikt M. Beckmann

  • Article
    | Open Access

    The RNA-binding protein MARF1 is required for post-transcriptional regulation of mRNAs during mouse oogenesis. Here, by analyzing a Drosophila MARF1 mutant, the authors show that MARF1 recruits CCR4-NOT deadenylase to shorten the poly-A tails of target mRNAs such as cyclin A and suppress their translation during Drosophila oogenesis.

    • Li Zhu
    • , Suresh K. Kandasamy
    •  & Ryuya Fukunaga

  • Article
    | Open Access

    UPF1 is a highly processive helicase that plays an essential role in nonsense-mediated mRNA decay. Here the authors use single molecule binding assays to establish a functionally important relationship between helicase grip to nucleic acids, binding lifetime and the duration of translocation.

    • Joanne Kanaan
    • , Saurabh Raj
    •  & Hervé Le Hir

  • Article
    | Open Access

    Ribosomal proteins are transported to the nucleus with the help of importins, from which they are released prior to incorporation into the nascent ribosome. Here the authors report the NMR structure of the ribosomal protein eS26 in complex with the escortin Tsr2 and shed light on the mechanism of eS26 release from importin.

    • Sabina Schütz
    • , Erich Michel
    •  & Vikram Govind Panse

  • Article
    | Open Access

    RNA–protein interactions often depend on the recognition of extended RNA elements but the identification of these motifs is challenging. Here, the authors present a global integrated approach to analyze RNA–protein binding landscapes, mapping extended RNA interaction motifs for four RNA-binding proteins.

    • Qin Zhou
    • , Nikesh Kunder
    •  & Zachary T. Campbell

  • Article
    | Open Access

    Mutations in the RNA component TERC can cause telomerase dysfunction but the underlying mechanisms are largely unknown. Here, the authors show that RNA-binding protein HuR regulates telomerase function by enhancing the methylation of TERC, which is impaired by several disease-relevant TERC mutations.

    • Hao Tang
    • , Hu Wang
    •  & Wengong Wang

  • Article
    | Open Access

    It remains poorly understood how a single RNA-binding protein recognizes diverse RNA targets. Here the authors use an integrative approach to study the binding of spliceosomal SNF protein to U1 and U2 small nuclear RNAs in the presence or absence of auxiliary protein U2A’ and show how SNF’s conformational dynamics are tuned to recognize different stem-loop structures.

    • Gert Weber
    • , Gregory T. DeKoster
    •  & Markus C. Wahl

  • Article
    | Open Access

    Arsenic resistance protein 2 (ARS2) plays an important role in nuclear RNA metabolism and interacts with the nuclear cap-binding complex (CBC). Here the authors present the human ARS2 structure and identify regions important for its interactions with binding partners supporting that mutually exclusive higher order CBC-ARS2 complexes are formed.

    • Wiebke Manuela Schulze
    • , Frank Stein
    •  & Stephen Cusack

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