Abstract：
:RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b, a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Li H,Lai P,Jia J,Song Y,Xia Q,Huang K,He N,Ping W,Chen J,Yang Z,Li J,Yao M,Dong X,Zhao J,Hou C,Esteban MA,Gao S,Pei D,Hutchins AP,Yao Hdoi
10.1016/j.stem.2016.12.002subject
Has Abstractpub_date
2017-04-06 00:00:00pages
462-477.e6issue
4eissn
1934-5909issn
1875-9777pii
S1934-5909(16)30458-1journal_volume
20pub_type
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