Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Area of Science:

• Molecular Biology
• RNA Biology
• Gene Regulation

Background:

• C/D box small nucleolar RNAs (SNORDs) are noncoding RNAs primarily known for guiding fibrillarin to rRNA for 2 -O-methylation.
• Canonical SNORDs function in the insoluble nuclear fraction associated with rRNA processing.

Purpose of the Study:

• To investigate the unexpected localization of SNORDs, including SNORD27, in soluble nuclear extracts.
• To elucidate the novel functions of SNORD27 beyond rRNA modification, particularly its role in pre-mRNA processing.

Main Methods:

• Native soluble nuclear extract preparation and analysis.
• RNA-RNA interaction studies to identify SNORD27 binding partners.
• Gene knockdown experiments to assess the impact on alternative splicing.

Main Results:

• A subset of SNORDs, including SNORD27, exists in a protein complex independent of fibrillarin in soluble nuclear extracts.
• SNORD27 regulates the alternative splicing of E2F7 pre-mRNA through direct RNA-RNA interaction, competing with U1 snRNP.
• SNORD27 knockdown activates silent exons in other genes via base complementarity, indicating a broader role in splicing regulation.

Conclusions:

• SNORDs possess a dual function, participating in both rRNA modification and pre-mRNA alternative splicing.
• This expands the known repertoire of splicing regulators and links rRNA and pre-mRNA processing pathways.
• SNORD27 acts as a splicing regulator through mechanisms distinct from its canonical rRNA methyltransferase-targeting role.