TY - JOUR T1 - Systematic discovery of endogenous human ribonucleoprotein complexes JF - bioRxiv DO - 10.1101/480061 SP - 480061 AU - Anna L. Mallam AU - Wisath Sae-Lee AU - Jeffrey M. Schaub AU - Fan Tu AU - Anna Battenhouse AU - Yu Jin Jang AU - Jonghwan Kim AU - Ilya J. Finkelstein AU - Edward M. Marcotte AU - Kevin Drew Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/11/27/480061.abstract N2 - Ribonucleoprotein (RNP) complexes are important for many cellular functions but their prevalence has not been systematically investigated. We developed a proteome-wide fractionation-mass-spectrometry strategy called differential fractionation (DIF-FRAC) to discover RNP complexes by their sensitivity to RNase A treatment. Applying this to human cells reveals a set of 115 highly-stable endogenous RNPs, and a further 1,428 protein complexes whose subunits associate with RNA, thus indicating over 20% of all complexes are RNPs. We show RNP complexes either dissociate, change composition, or form stable protein-only complexes upon RNase A treatment, uncovering the biochemical role of RNA in complex formation. We combine these data into a resource, rna.MAP (rna.proteincomplexes.org), which demonstrates that well-studied complexes such as replication factor C (RFC) and centralspindlin exist as RNP complexes, providing new insight into their cellular functions. We apply our method to red blood cells and mouse embryonic stem cells to demonstrate its ability to identify cell-type specific roles for RNP complexes in diverse systems. Thus the methodology has the potential uncover RNP complexes in different human tissues, disease states and throughout all domains of life.Summary An exploration of human protein complexes in the presence and absence of RNA reveals endogenous ribonucleoprotein complexes ER -