Institute of Botany, Chinese Academy of Sciences Analyzes the Mechanism of RNA Methylation Regulating Fruit Ripening
DNA methylation (5mC) and RNA methylation (m6A) are two important nucleic acid modifications that play important roles in gene expression regulation and are involved in many biological processes. However, it is unclear whether there is an intrinsic association between the two nucleic acid modifications. Recently, Qin Guozheng Research Group of the Institute of Botany, Chinese Academy of Sciences and Tian Shiping research team have revealed that DNA methylation can affect the m6A modification of tomato fruit by regulating the expression of m6A demethylase gene, while m6A demethylase feedback Regulate DNA methylation to collectively regulate fruit ripening.
Fruit ripening is a very complex process that is influenced by internal and external factors. Analyze the mature regulation mechanism, not only can theoretically recognize the important stage of plant development, but also provide a basis for improving fruit quality and prolonging storage and preservation time. Fruit ripening is finely regulated. Recent studies have shown that epigenetic regulation plays an important role in fruit ripening, and the expression of a large number of mature related genes is related to DNA methylation status. Mutation of the DNA demethylase gene SlDML2 will result in genome-scale DNA hypermethylation and significantly inhibit fruit ripening. As a conservative epigenetic modification, DNA methylation functions primarily by affecting the transcription of genes. In addition, it has also been reported that DNA methylation regulates variable splicing of mRNA, which in turn affects gene expression at the post-transcriptional level. However, whether DNA methylation affects m6A is not clear.
m6A is the most abundant modification method on mRNA, and is widely found in eukaryotes such as animals, plants, fruit flies and yeast. m6A modification plays multiple roles in mRNA metabolism, including mRNA stability, cleavage, translation efficiency, and nuclear export. There is increasing evidence that m6A modifications affect development and other important biological processes such as cancer stem cell proliferation, embryo and post-embryonic development, and circadian rhythms. Similar to DNA methylation, the m6A modification is catalyzed by methyltransferase and removed by demethylase. At present, little is known about how m6A modification is regulated. In addition, the physiological process of m6A modification involved in horticultural crops is not clear.
By comparing the m6A methylome changes at different maturity stages of tomato fruit, and the m6A methyl group differences in wild-type and mature-deficient mutant Cnr (spontaneous mutation; genomic-scale DNA hypermethylation), the researchers found m6A modification showed a dynamic trend during fruit ripening. The overall level of m6A decreased with the maturity of the fruit, similar to DNA methylation; in the mature defect mutant Cnr, accompanied by DNA hypermethylation, the overall level of m6A Also higher.
The researchers also found that m6A modifications are ubiquitous in tomato fruit mRNA, mainly in the vicinity of the stop codon and the 3' untranslated region (3'UTR). Overall, m6A modification was inversely correlated with gene transcription levels. The fruit maturation process and the change of the overall level of m6A in the Cnr mutant were related to the expression of the m6A demethylase gene SlALKBH2; SlALKBH2 was regulated by DNA methylation. The m6A demethylase S1ALKBH2 binds to the mRNA of the DNA demethylase gene SlDML2, regulating its m6A modification and stability. After the SlALKBH2 gene mutation, the m6A level of SlDML2 increased, the mRNA content decreased, and the fruit could not mature normally.
In summary, the study preliminarily identified the intrinsic association between DNA methylation and RNA methylation, revealing a new mechanism for fruit maturation regulation, and providing new ideas for elucidating mature regulatory networks. Given the multiple functions of DNA methylation and RNA methylation, the feedback regulation mechanisms presented in this study are also applicable to other biological processes.
The research results were published online August 6 in the international academic journal Genome Biology. Zhou Leilei, a Ph.D. student of Qin Guozheng Research Group, is the first author of the paper. Researchers Qin Guozheng and Tian Shiping are co-authors. The research was funded by the National Natural Science Foundation of China and the Chinese Academy of Sciences Youth Innovation Promotion Association.
