Developmental mRNA m(5)C landscape and regulatory innovations of massive m(5)C modification of maternal mRNAs in animals.
Developmental mRNA m(5)C landscape and regulatory innovations of massive m(5)C modification of maternal mRNAs in animals.
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DOI：
10.1038/s41467-022-30210-0
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发表时间：
2022-05-05
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
m5 C是已知时间最长的RNA修饰之一，然而，其在mRNA中的发育动力学、功能和进化在很大程度上仍然未知。在这里，我们在6种脊椎动物和无脊椎动物的不同发育阶段生成了定量mRNA m5 C图谱，并发现了由NSUN 2和NSUN 6介导的母体mRNA的会聚和意想不到的大规模甲基化。以果蝇为模型，我们揭示了缺乏母体mRNA m5 C的胚胎经历细胞周期延迟，未能及时启动母体到合子的过渡，这意味着母体mRNA m5 C的功能重要性。从无脊椎动物到人类，观察到两波m5 C调控创新：高等动物在mRNA的5'端获得顺式定向的NSUN 2介导的m5 C位点，伴随着更结构化的5' UTR区域的出现;人类获得数千个反式定向的NSUN 6介导的m5 C位点，富含调节有丝分裂细胞周期的基因。总的来说，我们的研究突出了早期胚胎发育机制的存在和监管创新，并为阐明mRNA m5 C在生物学和疾病中的作用提供了关键资源。已知mRNA以低至中等水平被m5 C修饰。在这里，作者在6个物种的动物发育过程中生成了mRNA m5 C的图谱，并通过NSUN 2和NSUN 6鉴定了母体mRNA的会聚和意外的大规模甲基化。
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. mRNAs are known to be decorated with m5C at a low-to-medium level. Here, the authors generate atlases of mRNA m5C during animal development in 6 species and identify convergent and unexpected massive methylation of maternal mRNAs by NSUN2 and NSUN6.
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DOI：
10.1242/dev.167833
发表时间：
2018-11-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Boroviak T;Stirparo GG;Dietmann S;Hernando-Herraez I;Mohammed H;Reik W;Smith A;Sasaki E;Nichols J;Bertone P
通讯作者：
Bertone P
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1126/science.aad8711
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert WV;Bell TA;Schaening C
通讯作者：
Schaening C
影响因子：
12.3
作者：
Amort T;Rieder D;Wille A;Khokhlova-Cubberley D;Riml C;Trixl L;Jia XY;Micura R;Lusser A
通讯作者：
Lusser A
影响因子：
14.9
作者：
Boccaletto P;Stefaniak F;Ray A;Cappannini A;Mukherjee S;Purta E;Kurkowska M;Shirvanizadeh N;Destefanis E;Groza P;Avşar G;Romitelli A;Pir P;Dassi E;Conticello SG;Aguilo F;Bujnicki JM
通讯作者：
Bujnicki JM