Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation

N6-甲基腺苷 信使核糖核酸 翻译(生物学) 生物 细胞生物学 核糖核酸 RNA结合蛋白 应力颗粒 基因 平动调节 基因表达 遗传学 P-体 甲基化 甲基转移酶
作者
Huilin Huang,Hengyou Weng,Wenju Sun,Xi Qin,Hailing Shi,Huizhe Wu,Boxuan Zhao,Ana Mesquita,Chang Liu,Celvie L. Yuan,Yueh‐Chiang Hu,Stefan Hüttelmaier,Jennifer R. Skibbe,Rui Su,Xiaolan Deng,Lei Dong,Miao Sun,Chenying Li,Sigrid Nachtergaele,Yungui Wang
出处
期刊:Nature Cell Biology [Nature Portfolio]
卷期号:20 (3): 285-295 被引量:2192
标识
DOI:10.1038/s41556-018-0045-z
摘要

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Moreover, the K homology domains of IGF2BPs are required for their recognition of m6A and are critical for their oncogenic functions. Thus, our work reveals a different facet of the m6A-reading process that promotes mRNA stability and translation, and highlights the functional importance of IGF2BPs as m6A readers in post-transcriptional gene regulation and cancer biology. Huang et al. identify IGF2BPs as an additional class of N6-methyladenosine (m6A) reader proteins. They find that IGF2BPs selectively bind to m6A-containing mRNAs and promote their stability.
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