The mechanism of RNA methylation regulating gene translation discovered by Beijing Genomics Institute
[China Chemical Instrument Network Technology Frontier] Yang Yungui’s research group at the Key Laboratory of Precision Genomic Medicine and the Collaborative Innovation Center for Genetics and Development at the Beijing Institute of Genomics, Chinese Academy of Sciences, is studying the regulation of m6A methylation modification-binding proteins in regulating mRNA processing. In the process, the molecular mechanism of the code reader YTHDF3 in regulating mRNA translation was discovered. The research results were recently published online in the journal Cell Research under the title Cytoplasmic m6A reader YTHDF3 promotes mRNA translation.
The research team screened the interacting proteins of YTHDF3 and YTHDF1 through the tandem affinity precipitation method and found that the main interaction with them is the ribosomal 40S small protein. subunit proteins and the 60S large subunit protein. GST pull-down experiments demonstrated that YTHDF3 interacts with these ribosomal large and small subunit proteins. Further new protein synthesis experiments demonstrated that YTHDF3 can promote mRNA translation, and the reduction in translation levels caused by knocking down YTHDF3 can only be complemented by wild-type YTHDF3. Combining transcriptome and photo-cross-linking – RNA sequencing and bioinformatics technology, it was proved that YTHDF3 and YTHDF1 can affect their respective RNA binding abilities. It was also found that YTHDF3 promotes the translation efficiency of transcripts where YTHDF3 and YTHDF1 jointly combine, revealing the role of YTHDF3 and YTHDF1 in the translation process. co-regulatory effect.
Cell Research also published the research results of Professor He Chuan of the University of Chicago on YTHDF3 regulating mRNA translation and stability. These research results clarify the molecular mechanism of m6A reader YTHDF3 regulating mRNA translation, provide a basis for further research on the biological functions of m6A and RNA epigenetics, and provide a basis for research on normal physiology (such as stem cell stemness maintenance and differentiation) or abnormal pathological life. The molecular mechanisms associated with activities (such as malignant tumors, etc.) provide new research directions for epigenetic regulation.
This research is supported by the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences’ pilot projects.
