IGF2BP3 promotes mRNA degradation through internal m7G modification
Liu, Chang; Dou, Xiaoyang; Zhao, Yutao; Zhang, Linda; Zhang, Lisheng; Dai, Qing; Liu, Jun; Wu, Tong; Xiao, Yu; He, Chuan
2024
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Abstract

Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

Details

Title IGF2BP3 promotes mRNA degradation through internal m7G modification
Author Liu, Chang : University of Chicago
Dou, Xiaoyang : University of Chicago
Zhao, Yutao : University of Chicago
Zhang, Linda : University of Chicago
Zhang, Lisheng : University of Chicago : (http://orcid.org/0000-0003-1872-9978)
Dai, Qing : University of Chicago : (http://orcid.org/0000-0002-8578-1568)
Liu, Jun : Peking University : (http://orcid.org/0000-0002-2498-9963)
Wu, Tong : University of Chicago : (http://orcid.org/0000-0001-9968-9909)
Xiao, Yu : University of Chicago
He, Chuan : University of Chicago : (http://orcid.org/0000-0003-4319-7424)
Content Type Article
Published in Nature Communications
Identifier(s) DOI: https://doi.org/10.1038/s41467-024-51634-w
Data availability statement The data supporting the findings of this study are available from the corresponding authors upon request. m7G-MeRIP-seq in WT HepG2 cells, knockdown control cells, and METTL1 stable knockdown HepG2 cells, and m7G-seq in HepG2 cells were downloaded and re-analyzed in this study (GSE112276). The sequencing data produced in this study have been deposited in Gene Expression Ominibus (GEO) repository under the accession number GSE241222. The mass spectrometry proteomics data generated in this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD049390 and 10.6019/ PXD049390. The list of top proteins enriched by m7G probes based on the proteomics data are provided in Supplementary Data 1. The primers for dCas13b construction, guide RNA target sequences, and qPCR primers used in this study are summarized in Supplementary Data 2. Source data are provided with this paper.
Funding Information R01 HL155909
RM1 HG008935
Publication Date 2024-08-28
Language English
Copyright Statement

© The Author(s) 2024

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Record Appears in Biological Sciences Division > Biochemistry and Molecular Biology
Centers and Institutes > Institute for Biophysical Dynamics
Physical Sciences Division > Chemistry
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Record Created 2024-08-28

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