Ribosome profiling reveals dynamic translational landscape in HEK293T cells following X-ray irradiation

Jingyu Hou; Lei Yu; Canlan Wu; Saisai Wei; Xiangwei Gao

doi:10.1016/j.ygeno.2025.110987

Ribosome profiling reveals dynamic translational landscape in HEK293T cells following X-ray irradiation

Genomics. 2025 Jan 2:110987. doi: 10.1016/j.ygeno.2025.110987. Online ahead of print.

Authors

Jingyu Hou¹, Lei Yu¹, Canlan Wu¹, Saisai Wei², Xiangwei Gao³

Affiliations

¹ Department of Clinical Laboratory of Sir Run-Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.
² Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China. Electronic address: saisaiwei@zju.edu.cn.
³ Department of Clinical Laboratory of Sir Run-Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: xiangweigao@zju.edu.cn.

PMID: 39755339
DOI: 10.1016/j.ygeno.2025.110987

Abstract

X-ray irradiation induces widespread changes in gene expression. Positioned at the bottom of the central dogma, translational regulation responds swiftly to environmental stimuli, fine-tuning protein levels. However, the global view of mRNA translation following X-ray exposure remains unclear. In this study, we systematically investigated X-ray-induced translational alternation using ribosome profiling. Our study revealed a temporary translation inhibition in HEK293T cells following X-ray treatment. A subset of mRNAs experienced translational upregulation by bypassing upstream open reading frames (uORFs). The upregulated genes were enriched in the MAPK signaling pathway, such as MAPKBP1. Suppression of MAPKBP1 inhibited X-ray-induced cell apoptosis. Furthermore, we identified the induction of novel peptides encoded by small open reading frames (smORFs) within long non-coding RNAs (lncRNAs) upon X-ray treatment. Overall, our findings provide a comprehensive overview of the translational landscape within eukaryotic cells following X-ray treatment, offering new insights into DNA damage response.

Keywords: Cell apoptosis; Ribosome profiling; X-ray; mRNA translation; smORF; uORF.