RNA-binding proteins in Mendelian disease

Alfredo Castello, Bernd Fischer, Matthias W. Hentze, Thomas Preiss*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    192 Citations (Scopus)

    Abstract

    RNA-binding proteins (RBPs) control all aspects of RNA fate, and defects in their function underlie a broad spectrum of human pathologies. We focus here on two recent studies that uncovered the in vivo mRNA interactomes of human cells, jointly implicating over 1100 proteins in RNA binding. Surprisingly, over 350 of these RBPs had no prior RNA binding-related annotation or domain homology. The datasets also contain many proteins that, when mutated, cause Mendelian diseases, prominently neurological, sensory, and muscular disorders and cancers. Disease mutations in these proteins occur throughout their domain architectures and many are found in non-classical RNA-binding domains and in disordered regions. In some cases, mutations might cause disease through perturbing previously unknown RNA-related protein functions. These studies have thus expanded our knowledge of RBPs and their role in genetic diseases. We also expect that mRNA interactome capture approaches will aid further exploration of RNA systems biology in varied physiological and pathophysiological settings.

    Original languageEnglish
    Pages (from-to)318-327
    Number of pages10
    JournalTrends in Genetics
    Volume29
    Issue number5
    DOIs
    Publication statusPublished - May 2013

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