N6-methyladenosine (m6A) is the most common post-transcriptional modification of eukaryotic mRNA, mediating more than 80% of RNA base methylation. This reversible mRNA methylation modification is very common and occurs at frequencies of about 3-5 residues / mRNA. The m6A study revealed a new field of gene regulation after eukaryotic transcription.
Prof. Chuan He, a professor at the University of Chicago, is an authoritative scientist in this field. His research team has recently made new progress in m6A research: they found that m6A mRNA methylation was played during transcription and in animal development An important role, this research results published in the February 13 issue of Nature magazine.
Professor He Chuan is mainly engaged in chemical biology, nucleic acid chemistry and biology, genetics and other aspects of the study. In recent years in the methylation modification, especially 5hmC and m6A and other aspects of access to many important findings. Has so far in Nature, Science and other international authoritative academic journals published a large number of papers. He has been awarded the American Cancer Research Young Scientist Award, the Keck Foundation Medical Research Outstanding Young Scholar Award and other awards, and was elected as the top life medicine research institute HHMI researcher.
Higher animals soon after fertilization, the protein production in the embryo relies on inherited mRNA from the female parent. But shortly thereafter, during the maternal-to-zygotic transition (MZT), when the embryo activates its own genome, it will undergo a profound change. This process is one of the most complex and precise coordination processes in early embryos of embryos, but so far scientists are not aware of the factors that affect the temporal pattern of vertebrate maternal-zygotic transition.
In this article, the researchers found that more than one-third of the zebrafish maternal mRNA can be regulated by N6 methyladenosine (m6A), and these parental mRNA cleavage processes are also performed by the m6A binding protein: Ythdf2 The Removal of Ythdf2 from zebrafish embryos slows down the decay of m6A-modified parental mRNA and prevents zygotic genome activation. Embryo can not start MZT in time, it will cause cell cycle pause, so the entire larvae development delay.
This study revealed a previously unknown mechanism of action: m6A-dependent RNA decay processes can regulate the clearance of maternal mRNA during zebrafish-zygotic transition, suggesting that m6A mRNA methylation is open in the transcriptome group as well as in animal development The process plays an important role.
At present, people have identified the specific identification of m6A protein, and its functional analysis. Previous studies have shown that m6A is a cell that accelerates mRNA metabolism and translates the modification. In the process of cell differentiation, embryonic development and stress response, m6A groups the mRNAs for processing, translation and decay, and then directs their respective fate. Professor He Chuan pointed out in his review article that m1A (N1-methyladenosine), m5C (5-methylcytosine), pseuduridine and m6A form an apparent transcription group, encoding a new level of protein synthesis.
M6A analysis method is mainly methyl-RNA immunoprecipitation and sequencing combined, known as MeRIP-Seq or m6A-Seq. This method can only locate m6A residues in the 100-200 nt transcribed region and can not identify the exact location of m6A at the level of the whole transcriptome. The Cornell University research team has published a new technology called miCLIP in the Nature Methods magazine. This technique can be very convenient to obtain single nucleotide resolution m6A map.
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