Integrative characterization of MYC RNA-binding function

Emerging evidence suggests that MYC interacts with RNAs. Here, we performed an integrative characterization of MYC as an RNA-binding protein in six cell lines. We found that MYC binds to a myriad of RNAs with high affinity for guanosine-rich RNAs. Global and specific depletion of RNAs reduces MYC chromatin occupancy. Mechanistically, two highly conserved sequences, amino acids 355-357 KRR and 364-367 RQRR, within the basic region of MYC are necessary for its RNA binding. Notably, alanine substitution of KRR abolishes MYC's RNA-binding ability both in vitro and in vivo, without affecting its ability to bind E-box DNA as part of the MYC:MAX dimer in vitro. The loss of RNA-binding function decreases MYC chromatin binding in vivo and attenuates its ability to promote gene expression, cell-cycle progression, and proliferation. Our study lays a foundation for future investigation into the role of RNAs in MYC-mediated transcriptional activation and oncogenic functions.

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Publication Details

Journal
Cell Genomics
Published
2025-05-15
DOI
https://doi.org/10.1016/j.xgen.2025.100878
Citations
3
Primary Topic
RNA and protein synthesis mechanisms
Type
article
Field-Weighted Citation Impact
2.42

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article

Integrative characterization of MYC RNA-binding function

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Cell Genomics
RNA and protein synthesis mechanisms
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article

Integrative characterization of MYC RNA-binding function

Avishek Bhuniya, Da Yang, Yongjie Huang, Junmei Wang, Luxuan Wang, Yuang Chen, Dhamotharan Pattarayan, Yang Liu, Xiaofei Wang, Zehua Wang, Min Zhang, Song Li, Yifei Wang, Sihan Li, Phuong L. Nguyen, Nara Lee, Haozhe Huang, Yu Zhang
article en
3 citations

Abstract

Emerging evidence suggests that MYC interacts with RNAs. Here, we performed an integrative characterization of MYC as an RNA-binding protein in six cell lines. We found that MYC binds to a myriad of RNAs with high affinity for guanosine-rich RNAs. Global and specific depletion of RNAs reduces MYC chromatin occupancy. Mechanistically, two highly conserved sequences, amino acids 355-357 KRR and 364-367 RQRR, within the basic region of MYC are necessary for its RNA binding. Notably, alanine substitution of KRR abolishes MYC's RNA-binding ability both in vitro and in vivo, without affecting its ability to bind E-box DNA as part of the MYC:MAX dimer in vitro. The loss of RNA-binding function decreases MYC chromatin binding in vivo and attenuates its ability to promote gene expression, cell-cycle progression, and proliferation. Our study lays a foundation for future investigation into the role of RNAs in MYC-mediated transcriptional activation and oncogenic functions.

Cell GenomicsVol. 5(7)
University of Pittsburgh (US), UPMC Hillman Cancer Center (US), University of Pittsburgh Medical Center (US), PharmacoGenetics (China) (CN)
American Cancer Society, University of Pittsburgh, Shear Family Foundation, National Institutes of Health, Cancer Institute, University of Pittsburgh, Center for Research Computing, University of Pittsburgh, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering
Zero hunger
Openalex Percentile: Top 12%
RNA and protein synthesis mechanisms
2.42
DOIOpen Access PDFOpenAlex
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