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Nat Commun 2022 May 05;131:2484. doi: 10.1038/s41467-022-30210-0.
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Developmental mRNA m5C landscape and regulatory innovations of massive m5C modification of maternal mRNAs in animals.

Liu J , Huang T , Chen W , Ding C , Zhao T , Zhao X , Cai B , Zhang Y , Li S , Zhang L , Xue M , He X , Ge W , Zhou C , Xu Y , Zhang R .

m5C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m5C maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using Drosophila as a model, we reveal that embryos lacking maternal mRNA m5C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m5C. From invertebrates to the lineage leading to humans, two waves of m5C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m5C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m5C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m5C in biology and disease.

PubMed ID: 35513466
Article link: Nat Commun

References [+] :
Abbasi-Moheb, Mutations in NSUN2 cause autosomal-recessive intellectual disability. 2012, Pubmed