A census of human RNA-binding proteins

Key Points Recent advances in next-generation sequencing methods and quantitative mass spectrometry have renewed the interest in RNA biology and the genome-wide investigation of post-transcriptional gene regulatory proteins. A global census that systematically lists the number of factors involved in post-transcriptional gene regulation (PTGR) is currently not available. Here, we provide an overall summary of the proteins involved in interactions with all classes of RNAs based on our current knowledge of PTGR; this will guide future systems-wide studies of PTGR. RNA-binding proteins (RBPs) are evolutionarily deeply conserved, and their structural domains diversified early in evolution. RBPs are among the most abundant proteins in the cell and are generally ubiquitously expressed, which mirrors their central and conserved role in gene regulation. Only ~2% of RBPs are tissue-specific, and most of these are mRNA- and non-coding RNA-binding proteins. Diseases involving RBPs show characteristic phenotypes depending on the type of RNA (for example, mRNA, ribosomal RNA and tRNA) predominantly bound by the RBPs. Correlated expression of RBPs across developmental processes can identify factors in shared PTGR pathways. Analyses of post-transcriptional gene regulation and the protein factors involved have been substantially driven forward by technological advances such as next-generation sequencing and modern protein mass spectrometry. This Analysis provides a census of 1,542 manually curated RNA-binding proteins, for which the authors have investigated interactions with different classes of RNA, evolutionary conservation, abundance and tissue-specific expression. Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabo