M6A modified the negative regulation of A-to-I editing and its mechanism.

Recently, the Chinese Academy of Sciences Institute of Biochemistry and Cell Biology Chen Lingling Research Group and the Chinese Academy of Sciences - Mapinstitute Institute of Computational Biology Yang Li research group, the n6-methyladenosines modulate A-to-I RNA editing, published in Molecular Cell, the study revealed two more The polymorphism between methylation (m6A) and adenosine to sub-janosinside base editing (A-to-I editing) at the position of adenosine-adenosine N6, which is prevalent, clarifies the negative regulatory effect of m6A modification on A-to-I editing and its mechanism.
so far, as many as 100 rna modifications have been found in the body, of which m6A modification and A-to-I editing are the epigenetic modifications of the two most common RNA levels present on (m) RNA, both of which occur on adenosine, A.
RNA epigenetic modification on both A's are very different in catalytic principles and occurrence locations: m6A is mainly catalyzed by methylaterase complexes (METTL3 and METTL14) and demethylated by demethylase (FTO and ALKBH5) reversible, mainly on the A-base of single-stranded RNA;
therefore, based on their differences in catalytic principles and locations, it is assumed that the two most common RNA epithests of m6A and A-to-I do not generally compete to occur at the same A base location.
whether there are other interactions between them is unclear.
in this work, the researchers used a systematic research method combining calculation and experiment to compare a-to-I editing of m6A-positive and m6A-negative RNA-seq data, revealing a certain negative correlation between m6A modification and A-to-I editing; A modification of the negative regulation of A-to-I editing, through the comparative analysis of multiple endogenous transcripts and the construction of report plasmids under normal conditions and METTL3/METTL14 double knock conditions, found that the binding capacity of ADAR1 and m6A-positive transcripts is weak, while the combination of ADAR1 and M6A negative transcripts is significantly improved when METTL3/METTL14 double knock suppression m6A, This suggests that the negative regulation of m6A modification to A-to-I editing may be achieved by regulating its binding ability with ADAR1.
research has been supported by the National Fund Committee, the Ministry of Science and Technology, the Chinese Academy of Sciences and the HHMI Foundation.
studies have revealed the dynamic change regulation of A-to-I editing in different transcription groups and the new role of A-to-I editing enzyme ADAR in the process of miRNA maturation, and this latest interoperability study between different RNA modifications provides new ideas and a new basis for the full disclosure of complex RNA epigenetic modification regulation.
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