Somatic cell reprogramming is another important breakthrough
January 19, the international academic journal 《cell stemcell》published online Chinese Academy of Sciences, Guangzhou Institute ofBiomedical and Health Yao Hongjie research group of the latest research results(RNAHelicaseDDX5InhibitsReprogrammingtoPluripotencybymiRNA-basedRepressionofRYBPanditsPRC1-dependentand-independentFunctions)。This article first reveals the important role of RNA bindingprotein (RBP) DDX5 in somatic cell reprogramming and regulation mechanisms,which will deepen the understanding of RBP-mediated cell fate decisions.
RBPs not only play an important role in maintaining intracellularhomeostasis, but also play an important role in differentiation and maintenanceof cell characteristics. Although the diversity and necessity of RBPs functionalmost involves all the processes of RNA metabolism, the mechanism of RBPs incell fate is to be further studied. In 2006, the Japanese scientist YamamotoYuki successfully established the induction of pluripotent stem cells (iPSCs)technology, to achieve the adult cells into a variety of differentiatedpotential of iPS cells, the guiding significance of clinical medicine, mountainstretch so won the 2012 Connaught Bell Physiology or Medicine Award. However,somatic cell reprogramming is a very complex process that must overcome theobstacles in order to reach the end and become a dry cell. In recent years,researchers are keen to explore one of the obstacles, epigenetic is one of theimportant factors. There have been many reports on the regulation of DNAmethylation, histone modification, microRNA and other epigenetic modificationsand transcription factors regulation of somatic cell reprogramming, but RBPsplay a role in cell fate, especially during somatic cell reprogramming Thefunction is not known.
Yao Hongjie research group found that reprogrammingprocess, although the expression of RBP DDX5 gradually increased, but it playsa role in restraining reprogramming. The lack of DDX5 function up-regulates theexpression levels of RING1 and YY1 binding proteins (RYBP) in nonclassical PRC1complexes by affecting the expression level of microRNA 125b. DDX5 dysfunctionand RYBP overexpression affect interstitial cells to epithelial cells at theearly stage of reprogramming and affect the activation of pluripotent genes atthe late reprogramming. It was found that DDY5 function was elevated in RYBP,which further promoted the level of ubiquitination (H2AK119ub1) of histone H2Alysine K119 site and promoted the enrichment of H2AK119ub1 into thetranscription initiation site of partial germline differentiation specific gene, And inhibit the expression of such genes.
The study team further found that RYBP is present in twocompletely different complexes and that part of RYBP is present in the samecomplex as multi-comb inhibitory complex 1 (PRC1 complex) and may play a rolein inhibiting partial germinal differentiation genes Another part of RYBP andpluripotency factor OCT4 exist in the same complex, play a role in geneactivation. In addition, the researchers found that RYBP in the genome of thebinding site in a large part of the binding site with OCT4 overlap, and RYBP isconducive to the recruitment of OCT4 to histone demethylase gene Kdm2b promoterregion, and activation The expression of endogenous pluripotent genes thuspromotes somatic cell reprogramming, which is a function of PRC1 independent.
This study reveals the important function of RBP DDX5 inthe regulation of somatic cell reprogramming and highlights the importance ofDdx5-microRNA-125b-Rybp upstream and downstream relationships in somatic cellreprogramming. This study first reveals the regulation of RNA-binding proteinsin somatic cell reprogramming, and reveals that crosstalk between RNA-bindingproteins and epigenetic information plays an important role in cell fatetransformation, a mechanism for cell fate transformation, and Technologydevelopment provides a new idea.
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