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

Cui, Li; Zheng, Jiarong; Lin, Yunfan; Lin, Pei; Lu, Ye; Zheng, Yucheng; Guo, Bing; Zhao, Xinyuan

doi:10.1002/ctm2.1705

Cited by 3 publications

(1 citation statement)

References 192 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The term 'onco-ribosome' refers to ribosomes that have undergone specific alterations in cancer cells that can be either programmed—part of the cell's oncogenic adaptation processes—or result from spontaneous mutations. Programmed changes are generally driven by oncogenic signals and include the selective dysregulation and modifications of RP, as well as chemical modifications in rRNA [reviewed in ( 80 , 81 )], that gear up the ribosome towards the synthesis of proteins favoring tumor progression. In contrast, spontaneous mutations may arise from genetic instability inherent in cancer cells, leading to aberrant ribosomal functions that further promote the malignant behaviour.…”

Section: Heterogeneity In Ribosomal Protein Composition Of Ribosomes:...mentioning

confidence: 99%

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease

Fuentes,

Pelletier,

Gentilella

2024

NAR Cancer

View full text Add to dashboard Cite

The ribosome is a remarkably complex machinery, at the interface with diverse cellular functions and processes. Evolutionarily conserved, yet intricately regulated, ribosomes play pivotal roles in decoding genetic information into the synthesis of proteins and in the generation of biomass critical for cellular physiological functions. Recent insights have revealed the existence of ribosome heterogeneity at multiple levels. Such heterogeneity extends to cancer, where aberrant ribosome biogenesis and function contribute to oncogenesis. This led to the emergence of the concept of ‘onco-ribosomes’, specific ribosomal variants with altered structural dynamics, contributing to cancer initiation and progression. Ribosomal proteins (RPs) are involved in many of these alterations, acting as critical factors for the translational reprogramming of cancer cells. In this review article, we highlight the roles of RPs in ribosome biogenesis, how mutations in RPs and their paralogues reshape the translational landscape, driving clonal evolution and therapeutic resistance. Furthermore, we present recent evidence providing new insights into post-translational modifications of RPs, such as ubiquitylation, UFMylation and phosphorylation, and how they regulate ribosome recycling, translational fidelity and cellular stress responses. Understanding the intricate interplay between ribosome complexity, heterogeneity and RP-mediated regulatory mechanisms in pathology offers profound insights into cancer biology and unveils novel therapeutic avenues targeting the translational machinery in cancer.

show abstract

Section: Heterogeneity In Ribosomal Protein Composition Of Ribosomes:...mentioning

confidence: 99%

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease

Fuentes,

Pelletier,

Gentilella

2024

NAR Cancer

View full text Add to dashboard Cite

show abstract

Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression

Lin,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing RNA stability, functionality, and interactions. To date, over 170 distinct RNA chemical modifications and more than 100 RNA‐modifying enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has been made in understanding RNA modification, the regulatory mechanisms that govern RNA‐modifying proteins themselves remain insufficiently explored. Post‐translational modifications (PTMs) such as phosphorylation, ubiquitination, and acetylation are crucial in modulating the function and behavior of these proteins. However, the full extent of PTM influence on RNA‐modifying proteins and their role in disease development remains to be fully elucidated. This review addresses these gaps by offering a comprehensive analysis of the roles PTMs play in regulating RNA‐modifying proteins. Mechanistic insights are provided into how these modifications alter biological processes, contribute to cellular function, and drive disease progression. In addition, the current research landscape is examined, highlighting the therapeutic potential of targeting PTMs on RNA‐modifying proteins for precision medicine. By advancing understanding of these regulatory networks, this review seeks to facilitate the development of more effective therapeutic strategies and inspire future research in the critical area of PTMs in RNA‐modifying proteins.

show abstract

Inconsistencies in the published rabbit ribosomal rRNAs: a proposal for uniformity in sequence and site numbering

De,

Zhou,

Brown

et al. 2024

Preprint

View full text Add to dashboard Cite

Examination of all publicly available Oryctolagus cuniculus (rabbit) ribosome cryo-EM structures reveals numerous confusing inconsistencies. First, there are a plethora of single nucleotide differences among the various rabbit 28S and 18S rRNA structures. Second, two nucleotides are absent from the NCBI Reference Sequence for the 18S rRNA gene. Moving forward, we propose using the Broad Institute's rabbit whole genome shotgun sequence and numbering to reduce modeling ambiguity and improve consistency between ribosome models.

show abstract

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

Cited by 3 publications

References 192 publications

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease

Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression

Inconsistencies in the published rabbit ribosomal rRNAs: a proposal for uniformity in sequence and site numbering

Contact Info

Product

Resources

About