Recognition of RNA N 6 -methyladenosine by IGF2BP proteins enhances mRNA stability and translation
Huilin Huang,Huilin Huang,Hengyou Weng,Hengyou Weng,Wen-Ju Sun,Xi Qin,Xi Qin,Hailing Shi,Hailing Shi,Huizhe Wu,Huizhe Wu,Huizhe Wu,Boxuan Simen Zhao,Boxuan Simen Zhao,Ana Mesquita,Chang Liu,Chang Liu,Celvie L. Yuan,Yueh-Chiang Hu,Stefan Hüttelmaier,Jennifer R. Skibbe,Rui Su,Rui Su,Xiaolan Deng,Xiaolan Deng,Xiaolan Deng,Lei Dong,Lei Dong,Miao Sun,Chenying Li,Chenying Li,Chenying Li,Sigrid Nachtergaele,Sigrid Nachtergaele,Yungui Wang,Yungui Wang,Chao Hu,Chao Hu,Kyle Ferchen,Kenneth D. Greis,Xi Jiang,Xi Jiang,Minjie Wei,Liang-Hu Qu,Jun-Lin Guan,Chuan He,Chuan He,Jian-Hua Yang,Jianjun Chen,Jianjun Chen +49 more
TLDR
This work reports the insulin-like growth factor 2 mRNA-binding proteins as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence, and identifies IGF2BPs as an additional class of N6-methyladenosine (m 6A) reader proteins.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.read more
Citations
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Journal ArticleDOI
Reading, writing and erasing mRNA methylation.
TL;DR: New and emerging methods to characterize and quantify the epitranscriptome are reviewed, and new concepts — in some cases, controversies — are discussed regarding the authors' understanding of the mechanisms and functions of m6A readers, writers and erasers are discussed.
Journal ArticleDOI
Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers
TL;DR: This review highlights recent progress in understanding the function of N6-methyladenosine (m6A), the most abundant internal mark on eukaryotic mRNA, in light of the specific biological contexts of m6A effectors, and emphasizes the importance of context for RNA modification regulation and function.
Journal ArticleDOI
Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism.
TL;DR: The current understanding of the m6A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, is described, with an emphasis on its role in regulating the isoform dosage of mRNAs.
Journal ArticleDOI
Functions of N6-methyladenosine and its role in cancer.
TL;DR: Al Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR and corresponding potential targets in cancer therapy are reviewed.
Journal ArticleDOI
RNA modifications modulate gene expression during development
TL;DR: Here, N6-methyladenosine affects the translation and stability of the modified transcripts, thus providing a mechanism to coordinate the regulation of groups of transcripts during cell state maintenance and transition and thereby facilitate proper development.
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