The international academic journal Cell Stem Cell published the latest research results of the research group of Yao Hongjie, the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences. This article first reveals the important role of RNA binding protein (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 intracellular homeostasis, but also play an important role in differentiation and maintenance of cell characteristics. Although the diversity and necessity of RBPs function almost involves all the processes of RNA metabolism, the mechanism of RBPs in cell fate is to be further studied. In 2006, the Japanese scientist Yamamoto Yuki successfully established the induction of pluripotent stem cells (iPSCs) technology, to achieve the adult cells into a variety of differentiated potential of iPS cells, the guiding significance of clinical medicine, mountain stretch so won the 2012 Connaught Bell Physiology or Medicine Award. However, somatic cell reprogramming is a very complex process that must overcome the obstacles 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 the important factors. There have been many reports on the regulation of DNA methylation, histone modification, microRNA and other epigenetic modifications and transcription factors regulation of somatic cell reprogramming, but RBPs play a role in cell fate, especially during somatic cell reprogramming The function is not known.
Yao Hongjie research group found that reprogramming process, although the expression of RBP DDX5 gradually increased, but it plays a role in restraining reprogramming. The lack of DDX5 function up-regulates the expression levels of RING1 and YY1 binding proteins (RYBP) in nonclassical PRC1 complexes by affecting the expression level of microRNA 125b. DDX5 dysfunction and RYBP overexpression affect interstitial cells to epithelial cells at the early stage of reprogramming and affect the activation of pluripotent genes at the late reprogramming. It was found that DDY5 function was elevated in RYBP, which further promoted the level of ubiquitination (H2AK119ub1) of histone H2A lysine K119 site and promoted the enrichment of H2AK119ub1 into the transcription 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 two completely different complexes, and that part of RYBP is present in the same complex with multi-comb inhibitory complex 1 (PRC1 complex), which may play a role in inhibiting partial germinal differentiation genes Another part of RYBP and pluripotency factor OCT4 exist in the same complex, play a role in gene activation. In addition, the researchers found that RYBP in the genome of the binding site in a large part of the binding site with OCT4 overlap, and RYBP is conducive to recruiting OCT4 to histone demethylase gene Kdm2b promoter region, and activation The expression of endogenous pluripotent genes thus promotes somatic cell reprogramming, which is a function of PRC1 independent.
This study reveals the important function of RBP DDX5 in the regulation of somatic cell reprogramming and highlights the importance of Ddx5-microRNA-125b-Rybp upstream and downstream relationships in somatic cell reprogramming. This study first reveals the regulation of RNA-binding proteins in somatic cell reprogramming, and reveals that crosstalk between RNA-binding proteins and epigenetic information plays an important role in cell fate transformation, a mechanism for cell fate transformation, and Technology development provides a new idea.