Systematic discovery of endogenous human ribonucleoprotein complexes

Anna L Mallam*, Wisath Sae-Lee, Jeffrey M Schaub, Fan Tu, Anna Battenhouse, Yu Jin Jang, Jonghwan Kim, John B. Wallingford, Ilya J Finkelstein, Edward M Marcotte† & Kevin Drew*† (* co-first authors) († co-corresponding), Cell Reports 29 (5) :1351-1368 (2019).
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RNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. Although recent studies have systematically identified individual RNA-binding proteins, their higher-order assembly into ribonucleoprotein (RNP) complexes has not been systematically investigated. Here, we describe a proteomics method for systematic identification of RNP complexes in human cells. We identify 1,428 protein complexes that associate with RNA, indicating that more than 20% of known human protein complexes contain RNA. To explore the role of RNA in the assembly of each complex, we identify complexes that dissociate, change composition, or form stable protein-only complexes in the absence of RNA. We use our method to systematically identify cell-type-specific RNA-associated proteins in mouse embryonic stem cells and finally, distribute our resource, rna.MAP, in an easy-to-use online interface ( Our system thus provides a methodology for explorations across human tissues, disease states, and throughout all domains of life.