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Zc3h13/Flacc 通过将 mRNA 结合因子 Rbm15/Spenito 桥接到 mA 机器组件 Wtap/Fl(2)d 来介导腺苷甲基化。

Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the mA machinery component Wtap/Fl(2)d.

机构信息

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

University of Basel, Basel 4002, Switzerland.

出版信息

Genes Dev. 2018 Mar 1;32(5-6):415-429. doi: 10.1101/gad.309146.117. Epub 2018 Mar 13.

DOI:10.1101/gad.309146.117
PMID:29535189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5900714/
Abstract

-methyladenosine (mA) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. mA is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of mA methyltransferase complex components in and mice. Like other components of this complex, Flacc controls mA levels and is involved in sex determination in We demonstrate that Flacc promotes mA deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the mA machinery.

摘要

m6A 是真核生物中最丰富的 mRNA 修饰，在多种生物过程中发挥着关键作用。m6A 由甲基转移酶样 3（Mettl3）的活性催化，该酶依赖于其他精确功能仍知之甚少的蛋白质。在这里，我们鉴定出 Zc3h13（锌指 CCCH 结构域蛋白 13）/Flacc [Fl（2）d 相关复合物成分] 作为 mA 甲基转移酶复合物成分在 和小鼠中的一个新的相互作用因子。像这个复合物的其他成分一样，Flacc 控制 m6A 水平，并参与 中的性别决定。我们证明 Flacc 通过将 Fl(2)d 桥接到 mRNA 结合因子 Nito 来促进 m6A 的沉积。总之，我们的工作推进了对 m6A 机制的保守性和调节的分子理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/24ff2dda0cd5/415f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/f12855802dcd/415f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/92da1d626a21/415f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/1e796fcb5c2c/415f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/b7d3e8ff99eb/415f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/ef9d78dd3278/415f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/b8114b3b57c2/415f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/24ff2dda0cd5/415f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/f12855802dcd/415f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/92da1d626a21/415f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/1e796fcb5c2c/415f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/b7d3e8ff99eb/415f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/ef9d78dd3278/415f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/b8114b3b57c2/415f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c465/5900714/24ff2dda0cd5/415f07.jpg

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