Decoding the molecular script of 2′-O-ribomethylation: Implications across CNS disorders

Abstract

Emerging evidence underscores the critical role of impaired mRNA translation in various neurobiological conditions. Ribosomal RNA (rRNA), essential for protein synthesis, undergoes crucial post-transcriptional modifications such as 2′-O-ribose methylation, pseudouridylation, and base modifications. These modifications, particularly 2′-O-ribose methylation is vital for stabilizing rRNA structures and optimizing translation efficiency by regulating RNA integrity and its interactions with proteins. Concentrated in key regions like decoding sites and the peptidyl transferase center, dysregulation of these modifications can disrupt ribosomal function, contributing to the pathogenesis of diverse neurological conditions, including mental health disorders, developmental abnormalities, and neurodegenerative diseases. Mechanistically, 2′-O-ribose methylation involves interactions between small nucleolar RNAs (snoRNAs), snoRNPs, and fibrillarin, forming a complex regulatory network crucial for maintaining ribosomal integrity and function. Recent research highlights the association of defective ribosome biogenesis with a spectrum of CNS disorders, emphasizing the importance of understanding rRNA mechanisms in disease pathology. This review focuses on the pivotal role of 2′-O-ribose methylation in shaping ribosomal function and its potential implications for unraveling the pathophysiology of CNS disorders. Insights gained from studying these RNA modifications could pave the way for new therapeutic strategies targeting ribosomal dysfunction and associated neuropathological conditions, advancing precision medicine and therapeutic interventions.

Keywords

• Ribosome
• 2′-O-Methylation
• Modification
• Translation
• Protein synthesis
• rRNA