SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells

Summary: m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs and is involved in many biological processes. METTL16 is a recently identified RNA m6A methyltransferase. However, how METTL16 activity is regulated remains poorly understood. Here, we report a previously unr...

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Main Authors: Haixia Li, Emma Wilkinson, Yan-Hong Cui, Ming Sun, Kenneth Lu, Seungwon Yang, Marc Bissonnette, Yu-Ying He
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725006977
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author Haixia Li
Emma Wilkinson
Yan-Hong Cui
Ming Sun
Kenneth Lu
Seungwon Yang
Marc Bissonnette
Yu-Ying He
author_facet Haixia Li
Emma Wilkinson
Yan-Hong Cui
Ming Sun
Kenneth Lu
Seungwon Yang
Marc Bissonnette
Yu-Ying He
author_sort Haixia Li
collection DOAJ
description Summary: m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs and is involved in many biological processes. METTL16 is a recently identified RNA m6A methyltransferase. However, how METTL16 activity is regulated remains poorly understood. Here, we report a previously unrecognized mechanism in regulating METTL16 activity. SSB not only serves as a co-factor for METTL16 in installing m6A RNA methylation by enhancing METTL16 binding to RNA but it also is a direct target of METTL16-mediated m6A RNA methylation, leading to a positive auto-regulatory loop that promotes m6A methylation, SSB expression, and chemoresistance in colorectal cancer cells. Our findings reveal the regulation of METTL16 activity by SSB, providing a basis for the development of future therapeutic strategies that target the METTL16/SSB axis in METTL16-dependent cancers such as colorectal cancer.
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issn 2211-1247
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publishDate 2025-07-01
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series Cell Reports
spelling doaj-art-e2f3bdfce414484f84f418dd1b25dbb42025-08-20T02:35:22ZengElsevierCell Reports2211-12472025-07-0144711592610.1016/j.celrep.2025.115926SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cellsHaixia Li0Emma Wilkinson1Yan-Hong Cui2Ming Sun3Kenneth Lu4Seungwon Yang5Marc Bissonnette6Yu-Ying He7Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Gastroenterology, Hepatology & Nutrition, University of Chicago, Chicago, IL, USADepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA; Corresponding authorSummary: m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs and is involved in many biological processes. METTL16 is a recently identified RNA m6A methyltransferase. However, how METTL16 activity is regulated remains poorly understood. Here, we report a previously unrecognized mechanism in regulating METTL16 activity. SSB not only serves as a co-factor for METTL16 in installing m6A RNA methylation by enhancing METTL16 binding to RNA but it also is a direct target of METTL16-mediated m6A RNA methylation, leading to a positive auto-regulatory loop that promotes m6A methylation, SSB expression, and chemoresistance in colorectal cancer cells. Our findings reveal the regulation of METTL16 activity by SSB, providing a basis for the development of future therapeutic strategies that target the METTL16/SSB axis in METTL16-dependent cancers such as colorectal cancer.http://www.sciencedirect.com/science/article/pii/S2211124725006977CP: CancerCP: Molecular biology
spellingShingle Haixia Li
Emma Wilkinson
Yan-Hong Cui
Ming Sun
Kenneth Lu
Seungwon Yang
Marc Bissonnette
Yu-Ying He
SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
Cell Reports
CP: Cancer
CP: Molecular biology
title SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
title_full SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
title_fullStr SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
title_full_unstemmed SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
title_short SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
title_sort ssb cooperates with mettl16 mediated m6a rna methylation to promote chemoresistance in colorectal cancer cells
topic CP: Cancer
CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124725006977
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