The sequence structure characteristics and dynamic changes of mRNA m5C are revealed

zhang Rui, a professor at Sun Yat-sen University's School of Life Sciences, revealed the precise positioning and dynamic changes of m5C modification in mRNA in mammalian cell lineages and tissues, and showed that m5C on mRNA has unique sequence and structural characteristics. The study was published May 7 in Nature-Structural and Molecular Biology.
Innsbruck, Austria, Professor Alexandra Lusser, in a commentary on the same period, "Getting a hold on cytosine methylation in mRNA", evaluated the new computational method developed by Zhang Rui's team to increase the accuracy of the m5C test and further provide convincing evidence of the tRNA methylation transfer enzyme NSUN2 mediated mRNA methylation.
it is understood that 5-methylcytosine (m5C) modifications are widely found in tRNA and rRNA, however, there is a great deal of controversy in the academic community about the existence of m5C modifications on mRNA. Through analysis, the study found that the currently reported "m5C" site is often clustered in high GC content areas, is not sensitive to RNA interference against NSUN2, and can not be rich in m5C antibodies, most likely the experimental introduction of false positive.
based on this feature, the study created a novel bio-informational computing process to filter noise and pinpoint m5C on mRNA. Through further analysis, the study found that NSUN2-dependent m5C bits tend to have a 3' rich G base sequence, usually located at the bottom of a small neck ring structure, highly consistent with their tRNA substrates, revealing the source of mRNA m5C sequences and structural characteristics.
the study found that in addition to NSUN2, other members of the NSUN family do not regulate mRNA m5C bits, suggesting that in addition to members of the NSUN family, new methyl transferases may be involved in catalysis of mRNA m5C bits that are not dependent on NSUN2. Through further sequencing analysis of transcription groups of 7 human tissues in 10 mouse tissues, 3212 and 2498 high confidence points were identified, respectively. The results showed that the number of mRNA m5C bits in different tissues was very different from the level of methylation. In the testes, liver, heart muscle and skeletal muscles of humans and mice, there are hundreds of high confidence m5C bits on mRNA, compared with few other tissues. In addition, these m5C site is not conservative between humans and mice, indicating that they are most likely cis-regulation.
this research and development method provides new tools for the study of mRNA m5C, and the precise map of mRNA m5C in mammals provides a solid foundation for the discovery of the regulation and function of m5C modification on mRNA.
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