The RNA-binding protein NOVA-1 regulates circRNA expression, alternative splicing, and aging in C. elegans

Area of Science:

• Molecular Biology
• Genetics
• Aging Research

Background:

• Circular RNAs (circRNAs) are regulated by RNA-binding proteins (RBPs), but their in vivo roles are not well understood.
• Previous studies showed age-associated circRNAs in C. elegans, with circ-crh-1 loss extending lifespan.
• The mammalian RBP NOVA2 promotes circRNA biogenesis, prompting investigation into its C. elegans homolog, NOVA-1.

Purpose of the Study:

• To investigate the in vivo role of NOVA-1 in regulating circRNA expression and function in C. elegans.
• To determine if NOVA-1 coordinates circRNA biogenesis with linear alternative splicing.
• To assess the impact of NOVA-1 on organismal lifespan and stress resilience.

Main Methods:

• RNA-sequencing of nova-1 mutants and wild-type C. elegans.
• Differential expression analysis of circRNAs and linear RNAs.
• Motif analysis of NOVA-1-regulated splicing events.

Main Results:

• NOVA-1 regulates 103 circRNAs, acting as a negative regulator for a subset.
• NOVA-1 influences linear alternative splicing, particularly 3' splice site usage and exon skipping.
• NOVA-1 mutants show extended lifespan and improved heat stress recovery.

Conclusions:

• NOVA-1 is a key regulator of circRNA expression and alternative splicing in C. elegans.
• NOVA-1 coordinates splicing regulation with circRNA production, exemplified by circ-crh-1.
• NOVA-1 activity influences C. elegans lifespan and stress resilience.