m5C in developmental stages

Three years!

In breif

We profiled mRNA m5C landscapes in developmental stages of human, mouse, frogs, zebrafish, and fly.
We found an unexpected strong enrichment of mRNA m5C in oocytes and early embryos.
The enrichment of m5C quickly vanish as the development progress.
The m5C sites are majorly contributed by NSUN2 and NSUN6.
In fruit fly, the deficiency of NSUN2 can lead to a slight delay in development.
The gain-and-loss of NSUN2-mediated sites can majorly come from cis-regulatory factors.
The unique innovation of NSUN6-mediated sites in human oocyte can come from a trans-regulation.

The story behind the article

See our three years’ struggle.

References

2022

Nat. Commun.

Developmental mRNA m5C landscape and regulatory innovations of massive m5C modification of maternal mRNAs in animals

Jianheng Liu , Tao Huang , Wanying Chen , and 13 more authors

Nature Communications, 2022

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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.