RNA associates with RNA-binding proteins (RBPs) from synthesis to decay, forming dynamic ribonucleoproteins that orchestrate gene expression. RBPs mediate crucial functions in RNA metabolism, including RNA synthesis, processing, transport, translation and degradation. Although essential for RNA life cycle, the repertoire of RBPs has remained largely unknown. The very recent development of a novel proteomic-based system-wide approach termed RNA interactome capture revealed the near-complete census of human RBPs. Applying UV cross-linking of proteins to RNA, oligo(dT) selection of poly(A) RNAs and quantitative mass spectrometry, this method not only ‘rediscovered’ most of the proteins already known to bind RNA, but added hundreds of novel members to the previously known repertoire of RBPs. The newly identified RBPs are distributed over a broad variety of protein families, participate in different biological processes and exert distinct protein functions, implying the existence of unprecedented links between RNA biology and intermediary metabolism, signalling, cellular homoeostasis or disease. Although the near-complete atlas of RBPs offered important insights into RNA biology, it also opened new functional and structural questions about protein–RNA interactions that remain to be answered.

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