Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins

Alfredo Castello, Bernd Fischer, Katrin Eichelbaum, Rastislav Horos, Benedikt M. Beckmann, Claudia Strein, Norman E. Davey, David T. Humphreys, Thomas Preiss, Lars M. Steinmetz, Jeroen Krijgsveld*, Matthias W. Hentze

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    1597 Citations (Scopus)

    Abstract

    RNA-binding proteins (RBPs) determine RNA fate from synthesis to decay. Employing two complementary protocols for covalent UV crosslinking of RBPs to RNA, we describe a systematic, unbiased, and comprehensive approach, termed "interactome capture," to define the mRNA interactome of proliferating human HeLa cells. We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria, adding more than 300 RBPs to those previously known and shedding light on RBPs in disease, RNA-binding enzymes of intermediary metabolism, RNA-binding kinases, and RNA-binding architectures. Unexpectedly, we find that many proteins of the HeLa mRNA interactome are highly intrinsically disordered and enriched in short repetitive amino acid motifs. Interactome capture is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings.

    Original languageEnglish
    Pages (from-to)1393-1406
    Number of pages14
    JournalCell
    Volume149
    Issue number6
    DOIs
    Publication statusPublished - 8 Jun 2012

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