作者
Huilin Huang,Hengyou Weng,Wenju Sun,Xi Qin,Hailing Shi,Huizhe Wu,Boxuan Simen 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,Chao Hu,Kyle Ferchen,Kenneth D. Greis,Xi Jiang,Minjie Wei,Liang‐Hu Qu,Jun‐Lin Guan,Chuan He,Jianhua Yang,Jianjun Chen
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.