m(6)A writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish
m(6)A writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish
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m(6)写入复合物促进斑马鱼视网膜祖细胞的及时分化和存活
DOI：
10.1016/j.bbrc.2021.06.043
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发表时间：
2021
影响因子：
3.1
通讯作者：
Chen Shuyi
中科院分区：
文献类型：
--
作者：
Huang Lianggui;Liang Huilin;Wang Sifeng;Chen Shuyi
N6-甲基腺苷（m6 A）是真核mRNA中最普遍的内部修饰，可调节mRNA代谢和功能。mRNAs上的大多数m6 A修饰由核心写入复合物催化，所述核心写入复合物由甲基转移酶Mettl 3和两个辅助组分Mettl 14和Wtap组成。最近的研究已经证明了m6 A在各种生理和病理过程中的重要作用，如干细胞多能性，细胞分化和癌症进展。然而，我们对视网膜中m6 A的了解仍然缺乏。在这项研究中，我们使用斑马鱼作为模型脊椎动物，研究视网膜发育过程中的m6 A修饰的功能。我们发现m6 A writer复合物的三个主要成分mettl 3、mettl 14和wtap在发育中的斑马鱼眼睛中大量表达，并且在斑马鱼胚胎中敲低m6 A writer复合物导致小眼形成、延迟视网膜祖细胞分化和增加细胞死亡。通过研究m6 A writer complex缺陷鱼的视网膜发育过程，我们表明m6 A修饰通过确保视网膜祖细胞的及时分化和存活来调节斑马鱼视网膜发育。
N6-Methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNAs that modulates mRNA metabolism and function. Most m6A modifications on mRNAs are catalyzed by a core writer complex consisting of a methyltransferase, Mettl3, and two ancillary components, Mettl14 and Wtap. Recent studies have demonstrated important roles of m6A in various physiological and pathological processes, such as stem cell multipotency, cell differentiation, and cancer progression. However, our knowledge about m6A in the retina is still lacking. In this study, we used zebrafish as a model vertebrate to study the function of the m6A modification during retinal development. We show that the three main components of the m6A writer complex,mettl3,mettl14andwtap, are abundantly expressed in the developing zebrafish eyes, and that knocking down m6A writer complex in zebrafish embryos caused microphthalmia formation, delayed retinal progenitor cells differentiation and increased cell death. By examining the retinal developmental processes in m6A writer complex-deficient fish, we show that m6A modification regulates zebrafish retinal development through ensuring the timely differentiation and survival of the retinal progenitor cells.