Decoding the ribosome’s hidden language - rRNA modifications as key players in cancer dynamics and targeted therapies

Sep 21, 2026

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Ribosomal RNA (rRNA) modifications are essential to ribosome structure and function and strongly influence cellular proteomics and cancer biology. Chemical modifications extend beyond structural roles by shaping ribosome functionality and cellular protein profiles. The review discusses how rRNA modifications regulate rRNA activity as well as wider cellular physiological processes, including shifts in translational output that can promote oncogenesis. It emphasizes mitochondrial rRNA modifications, where aberrant expression contributes to metabolic dysfunction and resistance to apoptosis. Challenges and future directions for targeting rRNA modifications are also evaluated, positioning them as a promising therapeutic frontier.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Overview of rRNA modifications and cellular regulation

Graphical Abstract

Influence on ribosome function and cancer development

Mitochondrial rRNA modifications and cancer cell traits

Therapeutic targeting opportunities

DOI: 10.1002/ctm2.1705 REVIEW Decoding the ribosome’s hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies Li Cui1,2 ,† Jiarong Zheng3 ,† Yucheng Zheng1 Bing Guo3 Yunfan Lin1 ,† Pei Lin1 Xinyuan Zhao1 Ye Lu1 1 Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China 2 Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, USA 3 Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Li Cui and Xinyuan Zhao, Stomatological Hospital, School ofStomatology, Southern Medical University, Guangzhou, Guangdong, China. Email: [licui@smu.edu.cn](licui@smu.edu.cn and)[ and](licui@smu.edu.cn and)[ ](licui@smu.edu.cn and)[zhaoxinyuan1989@smu.edu.cn](zhaoxinyuan1989@smu.edu.cn) Graphical Abstract 1. rRNA modifications crucially influence ribosome function and cancer development, altering cellular protein synthesis and oncogenesis. 2. Mitochondrial rRNA modifications impact cancer cell traits, including metabolic dysfunction and resistance to apoptosis. 3. Targeting rRNA modifications presents potential therapeutic avenues in cancer treatment, posing challenges and opportunities for breakthroughs. Clin. Transl. Med. 2024;14:e1705 . [https://doi.org/10.1002/ctm2.1705](https://doi.org/10.1002/ctm2.1705) [wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2) DOI: 10.1002/ctm2.1705 REVIEW Decoding the ribosome’s hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies Li Cui1,2 ,† Jiarong Zheng3 ,† Yucheng Zheng1 Bing Guo3 Yunfan Lin1 ,† Pei Lin1 Xinyuan Zhao1 Ye Lu1 1 Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China 2 Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, USA 3 Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Li Cui and Xinyuan Zhao, Stomatological Hospital, School ofStomatology, Southern Medical University, Guangzhou, Guangdong, China. Email: [licui@smu.edu.cn](licui@smu.edu.cn and)[ and](licui@smu.edu.cn and)[ ](licui@smu.edu.cn and)[zhaoxinyuan1989@smu.edu.cn](zhaoxinyuan1989@smu.edu.cn) †Equal contributors. Funding information National Natural Science Foundation of China, Grant/Award Numbers: 81901006, 82372905; Young Top-notch Talent of Pearl River Talent Plan, Grant/Award Number: 0920220228; Guangdong Provincial Science and Technology Project Foundation, Grant/Award Number: 2022A0505050038; Science Research Cultivation Program ofStomatological Hospital, Southern Medical University, Grant/Award Numbers: PY2020002, PY2022019 Abstract Ribosomal RNA (rRNA) modifications, essential components of ribosome structure and function, significantly impact cellular proteomics and cancer biology. These chemical modifications transcend structural roles, critically shaping ribosome functionality and influencing cellular protein profiles. In this review, the mechanisms by which rRNA modifications regulate both rRNA functions and broader cellular physiological processes are critically discussed. Importantly, by altering the translational output, rRNA modifications can shift the cellular equilibrium towards oncogenesis, thus playing a key role in cancer development and progression. Moreover, a special focus is placed on the functions of mitochondrial rRNA modifications and their aberrant expression in cancer, an area with profound implications yet largely uncharted. Dysregulation in these modifications can lead to metabolic dysfunction and apoptosis resistance, hallmark traits of cancer cells. Furthermore, the current challenges and future perspectives in targeting rRNA modifications are highlighted as a therapeutic approach for ca

FAQs

What is the main focus of this review?

The review focuses on how rRNA modifications decode a “hidden language” that regulates ribosome function and contributes to cancer dynamics and targeted therapies.

How do rRNA modifications affect cancer development?

By altering translational output and cellular equilibrium, rRNA modifications can shift processes toward oncogenesis and influence tumor progression.

Why are mitochondrial rRNA modifications emphasized?

Mitochondrial rRNA modifications and their aberrant expression in cancer are linked to metabolic dysfunction and resistance to apoptosis, with therapeutic implications that remain incompletely explored.

Sep 21, 2026

Uploaded by Ivy