Language
English
Publication Date
2-25-2025
Journal
Genome Biology
DOI
10.1186/s13059-025-03508-7
PMID
40001124
PMCID
PMC11863803
PubMedCentral® Posted Date
2-25-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited.
Results: We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA-binding proteins as baits. Using core snoRNA-binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While some of these interactions result in chemical modification, others may have modification-independent functions. We showed that snoRNA ribonucleoprotein complexes containing certain accessory proteins, like WDR43 and NOLC1, enriched for specific subsets of snoRNA-target RNA interactions with distinct roles in ribosome and spliceosome biogenesis. Notably, we discovered that SNORD89 guides 2'-O-methylation at two neighboring sites in U2 snRNA that fine-tune splice site recognition.
Conclusions: Chimeric eCLIP of snoRNA-associating proteins enables a comprehensive framework for studying snoRNA-target interactions in an RNA-binding protein-dependent manner, revealing novel interactions and regulatory roles in RNA biogenesis.
Keywords
RNA, Small Nucleolar, Humans, RNA-Binding Proteins, Animals, Mice, RNA, Ribosomal, Spliceosomes, RNA, Small Nuclear
Published Open-Access
yes
Recommended Citation
Song, Zhuoyi; Bae, Bongmin; Schnabl, Simon; et al., "Mapping snoRNA-Target RNA Interactions in an RNA-Binding Protein-Dependent Manner With Chimeric eCLIP" (2025). Faculty and Staff Publications. 3848.
https://digitalcommons.library.tmc.edu/baylor_docs/3848