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

H Huang, H Weng, W Sun, X Qin, H Shi, H Wu… - Nature cell …, 2018 - nature.com
H Huang, H Weng, W Sun, X Qin, H Shi, H Wu, BS Zhao, A Mesquita, C Liu, CL Yuan, YC Hu
Nature cell biology, 2018nature.com
Abstract N 6-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 …
Abstract
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.
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