N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.
N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.
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DOI：
10.1093/nar/gkx141
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发表时间：
2017-06-02
影响因子：
14.9
通讯作者：
Pan T
中科院分区：
文献类型：
--
作者：
Liu N;Zhou KI;Parisien M;Dai Q;Diatchenko L;Pan T
N-6-甲基腺苷（m6 A）是真核生物信使RNA（mRNA）中最丰富的内部修饰，几乎影响mRNA生命周期的各个阶段。YTH结构域蛋白可以特异性识别m6 A修饰，以控制mRNA的成熟、翻译和降解。m6 A还可以改变RNA结构，影响细胞中RNA-蛋白质相互作用。在这里，我们表明，m6 A增加了其周围的RNA序列结合异质核核糖核蛋白G（HNRNPG）的可及性。此外，HNRNPG通过其C-末端低复杂性区域结合m6 A-甲基化RNA，其在体外自组装成大颗粒。低复杂性区域内的Arg-Gly-Gly重复序列是与m6 A甲基化暴露的RNA基序结合所必需的。我们在转录组中鉴定了13，191个m6 A位点，这些位点调节RNA-HNRNPG相互作用，从而改变靶mRNA的表达和选择性剪接模式。低复杂性区域在mRNA结合蛋白中普遍存在。我们的研究结果表明，m6 A依赖的RNA结构改变可以促进m6 A修饰的RNA直接结合到RNA结合蛋白的低复杂性区域。
N 6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA–protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro. The Arg-Gly-Gly repeats within the low-complexity region are required for binding to the RNA motif exposed by m6A methylation. We identified 13,191 m6A sites in the transcriptome that regulate RNA–HNRNPG interaction and thereby alter the expression and alternative splicing pattern of target mRNAs. Low-complexity regions are pervasive among mRNA binding proteins. Our results show that m6A-dependent RNA structural alterations can promote direct binding of m6A-modified RNAs to low-complexity regions in RNA binding proteins.