Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers.
Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers.
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DOI：
10.1093/nar/gkad534
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发表时间：
2023-09-08
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
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m6A甲基化在生物体发育中提供了重要的调控层，并且在一系列癌症和神经病理学中是异常的。由m6A甲基化编码的信息通过识别甲基化位点的RNA结合蛋白（m6A阅读器）整合到现有的RNA调控网络中。m6A阅读器包括一类特征明确的专用蛋白质，YTH蛋白质，以及一组更广泛的多功能调节剂，其中m6A的识别仅部分了解。在这种认识的分子洞察力是必不可少的，以建立一个机制的理解全球m6A调节。在这项研究中，我们表明，读取器IMP 1使用一个专用的疏水平台识别m6A，该平台在甲基部分上组装，产生稳定的高亲和力相互作用。这种识别在整个进化过程中是保守的，并且独立于潜在的序列背景，但基于IMP 1对GGAC RNA的强序列特异性。这使我们提出了一个概念m6A调控甲基化在识别选定的IMP1目标，这是依赖于可用的IMP1的细胞浓度，不同于观察到的YTH蛋白的上下文依赖性的作用。
m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins.
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影响因子：
4.8
作者：
Huppertz, Ina;Attig, Jan;D'Ambrogio, Andrea;Easton, Laura E.;Sibley, Christopher R.;Sugimoto, Yoichiro;Tajnik, Mojca;Koenig, Julian;Ule, Jernej
通讯作者：
Ule, Jernej
影响因子：
8.8
作者：
Conway AE;Van Nostrand EL;Pratt GA;Aigner S;Wilbert ML;Sundararaman B;Freese P;Lambert NJ;Sathe S;Liang TY;Essex A;Landais S;Burge CB;Jones DL;Yeo GW
通讯作者：
Yeo GW
DOI：
10.1261/rna.079615.123
发表时间：
2023-06
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
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DOI：
10.1016/j.jmr.2011.09.004
发表时间：
2011-12-01
期刊：
Journal of magnetic resonance (San Diego, Calif. : 1997)
影响因子：
--
作者：
Kay, Lewis E;Ikura, Mitsuhiko;Bax, Ad
通讯作者：
Bax, Ad
DOI：
10.1126/science.1242939
发表时间：
2014-01-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Buxbaum AR;Wu B;Singer RH
通讯作者：
Singer RH