The m(6)A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5'-3' exoribonuclease XRN1.
The m(6)A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5'-3' exoribonuclease XRN1.
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DOI：
10.1261/rna.064238.117
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Bohnsack MT
中科院分区：
文献类型：
--
作者：
Kretschmer J;Rao H;Hackert P;Sloan KE;Höbartner C;Bohnsack MT
RNA中的N6-甲基腺苷（m6 A）修饰在调节基因表达的许多不同方面发挥重要作用。虽然m6 As可以对mRNA的结构、成熟或翻译具有直接影响，但这种修饰也可以通过被称为“阅读器”的蛋白质影响RNA的命运，所述蛋白质特异性识别并结合修饰的核苷酸。几种含有YTH结构域的蛋白质已被鉴定为调节特定mRNA的剪接、翻译或稳定性的m6 A阅读器。与其他含有YTH结构域的蛋白质相比，YTHDC 2具有几个定义的结构域，在这里，我们分析了这些结构域对YTHDC 2的RNA和蛋白质相互作用的贡献。YTHDC 2的YTH结构域通过保守的疏水口袋优先结合含m6 A的RNA，而锚蛋白重复序列介导与5′-3′核糖核酸外切酶XRN 1的RNA非依赖性相互作用。我们表明，YTH和R3 H结构域有助于YTHDC 2与细胞RNA的结合，并使用交联和cDNA分析（CRAC），我们揭示了YTHDC 2与小核糖体亚基在mRNA进入/退出位点附近相互作用。最近发现YTHDC 2促进特定mRNA的“快速通道”表达程序，我们的数据表明，YTHDC 2通过招募RNA降解机制来调节含m6 A的mRNA的稳定性，并通过利用其独特的RNA结合结构域来桥接含m6 A的mRNA和核糖体之间的相互作用，以促进其有效的翻译来实现这一点。
N6-methyladenosine (m6A) modifications in RNAs play important roles in regulating many different aspects of gene expression. While m6As can have direct effects on the structure, maturation, or translation of mRNAs, such modifications can also influence the fate of RNAs via proteins termed “readers” that specifically recognize and bind modified nucleotides. Several YTH domain-containing proteins have been identified as m6A readers that regulate the splicing, translation, or stability of specific mRNAs. In contrast to the other YTH domain-containing proteins, YTHDC2 has several defined domains and here, we have analyzed the contribution of these domains to the RNA and protein interactions of YTHDC2. The YTH domain of YTHDC2 preferentially binds m6A-containing RNAs via a conserved hydrophobic pocket, whereas the ankyrin repeats mediate an RNA-independent interaction with the 5′–3′ exoribonuclease XRN1. We show that the YTH and R3H domains contribute to the binding of YTHDC2 to cellular RNAs, and using crosslinking and analysis of cDNA (CRAC), we reveal that YTHDC2 interacts with the small ribosomal subunit in close proximity to the mRNA entry/exit sites. YTHDC2 was recently found to promote a “fast-track” expression program for specific mRNAs, and our data suggest that YTHDC2 accomplishes this by recruitment of the RNA degradation machinery to regulate the stability of m6A-containing mRNAs and by utilizing its distinct RNA-binding domains to bridge interactions between m6A-containing mRNAs and the ribosomes to facilitate their efficient translation.
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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
n（6） - 甲基腺苷依赖性RNA结构开关调节RNA蛋白质相互作用。
影响因子：
64.8
作者：
Liu, Nian;Dai, Qing;Zheng, Guanqun;He, Chuan;Parisien, Marc;Pan, Tao
通讯作者：
Pan, Tao
影响因子：
48
作者：
Linder, Bastian;Grozhik, Anya V.;Olarerin-George, Anthony O.;Meydan, Cem;Mason, Christopher E.;Jaffrey, Samie R.
通讯作者：
Jaffrey, Samie R.
影响因子：
64.8
作者：
Lence, Tina;Akhtar, Junaid;Roignant, Jean-Yves
通讯作者：
Roignant, Jean-Yves
影响因子：
10.5
作者：
Ke S;Alemu EA;Mertens C;Gantman EC;Fak JJ;Mele A;Haripal B;Zucker-Scharff I;Moore MJ;Park CY;Vågbø CB;Kusśnierczyk A;Klungland A;Darnell JE Jr;Darnell RB
通讯作者：
Darnell RB