Comprehensive Pan-Cancer Mutation Density Patterns in Enhancer RNA

Author:

Zhang Troy1ORCID,Yu Hui1,Jiang Limin1,Bai Yongsheng2ORCID,Liu Xiaoyi3,Guo Yan1ORCID

Affiliation:

1. Department of Public Health and Sciences, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA

2. Department of Biology, Eastern Michigan University, Ypsilanti, MI 48197, USA

3. Department of Computer Science, University of South Carolina, Columbia, SC 29208, USA

Abstract

Significant advances have been achieved in understanding the critical role of enhancer RNAs (eRNAs) in the complex field of gene regulation. However, notable uncertainty remains concerning the biology of eRNAs, highlighting the need for continued research to uncover their exact functions in cellular processes and diseases. We present a comprehensive study to scrutinize mutation density patterns, mutation strand bias, and mutation burden in eRNAs across multiple cancer types. Our findings reveal that eRNAs exhibit mutation strand bias akin to that observed in protein-coding RNAs. We also identified a novel pattern, in which mutation density is notably diminished around the central region of the eRNA, but conspicuously elevated towards both the beginning and end. This pattern can be potentially explained by a mechanism involving heightened transcriptional activity and the activation of transcription-coupled repair. The central regions of the eRNAs appear to be more conserved, hinting at a potential mechanism preserving their structural and functional integrity, while the extremities may be more susceptible to mutations due to increased exposure. The evolutionary trajectory of this mutational pattern suggests a nuanced adaptation in eRNAs, where stability at their core coexists with flexibility at their extremities, potentially facilitating their diverse interactions with other genetic entities.

Funder

National Cancer Institute

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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