Deciphering theRNA-bound proteome of human embryonic stem cells
RNA-binding proteins(RBPs) are essential regulators of post-transcriptional gene expression,controlling numerous aspects in the life of an RNA molecule. While remarkableprogress has been made in unveiling the transcriptional regulatory principlesunderlying pluripotency, relatively little is known about the role ofpost-transcriptional regulation in embryonic stem cells (ESCs). Here, wepresent the first mRNA-binding proteome of human ESCs (hESCs).Using a proteomic-based approach, we identified 810 high-confidence RBPs,including 168 candidate dual DNA and RNA binding proteins (DRBPs). We show thatRBPs are preferentially expressed in hESCs and dynamically regulated during exitfrom pluripotency. Notably, we found that many RBPs are bound by the coretranscriptional circuitry of ESCs, consisting of OCT4, SOX2 and NANOG.Knockdown of these three master regulators further indicated that RBPs arekey players in the pluripotency network. Finally, we determined the dualnucleic-acid-binding activity of two pluripotency factors, ESRP1 and STAT3.Taken together, our findings reveal that RBPs have a far greater role in theregulation of human pluripotency than previously appreciated.