Intronic small nucleolar RNAs regulate host gene splicing through base pairing with their adjacent intronic sequences

Area of Science:

• Molecular Biology
• RNA Biology
• Genetics

Background:

• Small nucleolar RNAs (snoRNAs) are noncoding RNAs primarily involved in rRNA maturation.
• Most mammalian snoRNAs are intronic, produced via host gene transcription and splicing.
• The regulatory role of intronic snoRNAs on host gene expression is largely unknown.

Purpose of the Study:

• To investigate the potential role of intronic snoRNAs in regulating host gene splicing.
• To explore the prevalence and mechanism of snoRNA-host RNA interactions in splicing control.

Main Methods:

• Computational analysis of human RNA-RNA interaction datasets.
• Investigated the SNORD2-EIF4A2 duplex as a model system.
• Utilized antisense oligonucleotides and mutations to disrupt snoRNA-intron structures.

Main Results:

• 30% of detected snoRNAs interact with host transcripts, often near alternative splice sites.
• The SNORD2 snoRNA interaction with its host (EIF4A2) intron hinders splicing of an alternative exon.
• Disrupting this interaction promotes alternative exon splicing and alters transcript ratios.

Conclusions:

• Intronic snoRNAs can act as regulators of their host gene's splicing.
• SnoRNA-host RNA duplexes near alternative exons suggest a widespread mechanism for splicing control.
• This study supports a broader role for intronic snoRNAs in regulating host transcript maturation.