The mechanism of m6A modified regulatory cell reprogramming is revealed

, a researcher at the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences, revealed the
A modifys the mechanism of regulating soliogenic cell reprogramming and provides a new perspective on understanding the function of m6A in the process of cell fate-determining such as soy cell reprogramming. The study was published online September 8 in Cell Reports.
m
。 A (N
-thyroid) is one of the most common and abundant chemical modifications in the post-transcriptional modification of the electron organism mRNA. The modification is jointly regulated by methyl transferase complexes (METTL3, METTL14, WTAP, etc.), demethylase (FTO and ALKBH5), and binding proteins (YTHDF1/2/3, YTHDC1/2, etc.) to participate in important physiological processes such as stem cell fate decision and embryonic development. Early studies have shown that m
A played an important role in the maintenance and differentiation of stem cell ernogeneity and somatic cell reprogramming, but the conclusions were different under different conditions.
in order to study the m-
more clearly A's role in somogenetic cell reprogramming, the researchers focused on the relatively single function of m
A binding protein YTHDF protein family. The results show that knocking down Ythdf2 or Ythdf3 during soytic cell reprogramming inhibits reprogramming, and this inhibition is m
A dependent, while knocking down Ythdf1 has little effect on the efficiency of reprogramming.
further studies have found that YTHDF2 reprogramms cells by recruiting CCR4-NOT deadenosine complex regulators, while YTHDF3 interacts with PAN3 to recruit PAN2-PAN3 complexes to de-adenosineize mRNA. In the reprogramming process, YTHDF2-CCR4-NOT and YTHDF3-PAN2-PAN3, two different mRNA degradation pathways, work together to promote the rapid removal of the somatic cell-related gene mRNA, which is beneficial to the transformation of gene expression network types from somatic cells to erythmatic stem cells. When either pathway is impaired, it can lead to longer expression of soy cell-related genes, thereby impairing reprogramming.
the study also found THATD2, an effect factor of the Hippo signaling pathway, to be one of the important target genes by screening genes with extended mRNA half-life after knocking down Ythdf2/3. TEAD2 combines and maintains gene expression associated with intersessional conversion (EMT) in the early stages of reprogramming, and over-expression of Tead2 inhibits the efficiency of reprogramming. Knocking down Ythdf2/3 will cause THED2 binding EMT-related gene expression to increase, and will promote cell migration, indicating that knocking Ythdf2/3 will promote the cell EMT process, so that cells can not carry out the MET process properly resulting in reprogramming efficiency is inhibited.
the study also restored normal reprogramming efficiency by knocking down Tad2 or the EMT-related gene Tgfb1. The study shows that the effect of m
A binding protein YTHDF protein family on cell fate transformation shows that YTHDF1/2/3 plays a different role in reprogramming, and confirms that YTHDF2 and YTHDF3 jointly regulate sodocyte reprogramming through different RNA degradation pathways. (Source: China Science Journal Zhu Hanbin Huang Boquan)
related paper information: