SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells
m<sup>6</sup>A RNA methylation is the most prevalent internal modification in mammalian mRNAs and is involved in many biological processes. METTL16 is a recently identified RNA m<sup>6</sup>A 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 m<sup>6</sup>A RNA methylation by enhancing METTL16 binding to RNA but it also is a direct target of METTL16-mediated m<sup>6</sup>A RNA methylation, leading to a positive auto-regulatory loop that promotes m<sup>6</sup>A 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.
Authors
- Seungwon Yang (ORCID: https://orcid.org/0000-0002-8970-7373)
- Kenneth Lu
- Marc Bissonnette (ORCID: https://orcid.org/0000-0001-8420-4294)
- Yu‐Ying He (ORCID: https://orcid.org/0000-0002-2665-7962)
- Yan‐Hong Cui (ORCID: https://orcid.org/0000-0002-4169-6521)
- Emma Wilkinson (ORCID: https://orcid.org/0000-0003-3468-0326)
- Haixia Li (ORCID: https://orcid.org/0000-0002-8442-071X)
- Ming Sun (ORCID: https://orcid.org/0000-0002-5948-2708)
Institutions
- University of Illinois Chicago (US)
- University of Chicago (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1016/j.celrep.2025.115926
- Citations
- 2
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Ohio State University
- University of Chicago
- National Institutes of Health
- National Institute of Environmental Health Sciences
- Comprehensive Cancer Center, University of Chicago Medical Center