m6A Topological Transition Coupled to Developmental Regulation of Gene Expression During Mammalian Tissue Development.
m6A Topological Transition Coupled to Developmental Regulation of Gene Expression During Mammalian Tissue Development.
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m6A 拓扑转变与哺乳动物组织发育过程中基因表达的发育调控相结合
DOI：
10.3389/fcell.2022.916423
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发表时间：
2022
影响因子：
5.5
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Li S;Yang Q;Jiao R;Xu P;Sun Y;Li X
N6-甲基腺苷（m6 A）是信使RNA（mRNA）中最常见的内部修饰和可逆的表观标记，在多种生物学过程中起着重要作用。然而，m6 A的动态分布模式及其在哺乳动物组织发育过程中的意义知之甚少。在这里，我们发现，基于m6 A的分布模式，蛋白质编码基因被分为五组具有显着不同的生物学特性和功能。引人注目的是，在胎儿和成年阶段之间的多个哺乳动物组织的m6 A甲基化组的比较揭示了在哺乳动物组织发育期间动态的m6 A拓扑转变，并且鉴定了大量在5′ UTR中具有显著m6 A丢失或在终止密码子周围具有m6 A增益的基因。5′ UTR中m6 A缺失的基因高度富集在发育阶段特异性基因中，其m6 A拓扑转换与组织发育过程中的基因表达调控密切相关。终止密码子周围m6 A增益的基因与组织特异性功能相关。我们的研究结果揭示了不同的m6 A拓扑结构之间的蛋白质编码基因，与不同的特点。更重要的是，这些具有m6 A拓扑转换的基因通过调控基因表达对组织发育至关重要，表明动态m6 A拓扑转换在哺乳动物组织发育过程中的重要性。
N6-methyladenosine (m6A) is the most prevalent internal modification and reversible epitranscriptomic mark in messenger RNAs (mRNAs) and plays essential roles in a variety of biological processes. However, the dynamic distribution patterns of m6A and their significance during mammalian tissue development are poorly understood. Here, we found that based on m6A distribution patterns, protein-coding genes were classified into five groups with significantly distinct biological features and functions. Strikingly, comparison of the m6A methylomes of multiple mammalian tissues between fetal and adult stages revealed dynamic m6A topological transition during mammalian tissue development, and identified large numbers of genes with significant m6A loss in 5′UTRs or m6A gain around stop codons. The genes with m6A loss in 5′UTRs were highly enriched in developmental stage-specific genes, and their m6A topological transitions were strongly associated with gene expression regulation during tissue development. The genes with m6A gain around the stop codons were associated with tissue-specific functions. Our findings revealed the existence of different m6A topologies among protein-coding genes that were associated with distinct characteristics. More importantly, these genes with m6A topological transitions were crucial for tissue development via regulation of gene expression, suggesting the importance of dynamic m6A topological transitions during mammalian tissue development.
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YTHDF2 通过直接招募 CCR4-NOT 去腺苷酶复合物来破坏含有 m(6)A 的 RNA 的稳定性。
影响因子：
16.6
作者：
Du, Hao;Zhao, Ya;He, Jinqiu;Zhang, Yao;Xi, Hairui;Liu, Mofang;Ma, Jinbiao;Wu, Ligang
通讯作者：
Wu, Ligang
影响因子：
2.7
作者：
Joeng KS;Schumacher CA;Zylstra-Diegel CR;Long F;Williams BO
通讯作者：
Williams BO
影响因子：
--
作者：
Court F;Arnaud P
通讯作者：
Arnaud P
影响因子：
23.9
作者：
Batista, Pedro J.;Molinie, Benoit;Wang, Jinkai;Qu, Kun;Zhang, Jiajing;Li, Lingjie;Bouley, Donna M.;Lujan, Ernesto;Haddad, Bahareh;Daneshvar, Kaveh;Carter, Ava C.;Flynn, Ryan A.;Zhou, Chan;Lim, Kok-Seong;Dedon, Peter;Wernig, Marius;Mullen, Alan C.;Xing, Yi;Giallourakis, Cosmas C.;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
4.4
作者：
Gu Z;Eils R;Schlesner M;Ishaque N
通讯作者：
Ishaque N