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Developmental mRNA mC landscape and regulatory innovations of massivemC modification of maternal mRNAs in animals.


Liu J. et al.

mC 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 mC 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 mC undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA mC. From invertebrates to the lineage leading to humans, two waves of mC regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated mC 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 mC 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 mC in biology and disease.

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Antibody

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Published
May, 2022

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Products used in this publication

  • Mouse IgG
    C15200003
    5-methylcytosine (5-mC) Antibody for ICC/IF

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