Poster abstracts
Poster number 134 submitted by Sampurna Dutta
Role of ADR-1 in maintaining RNA homeostasis and promoting longevity
Sampurna Dutta (Genome, Cell and Developmental Biology, Indiana University Bloomington), Heather A. Hundley (Department of Biology, Indiana University Bloomington)
Abstract:
Physiological aging causes widespread disruptions in post-transcriptional RNA processing, modifications, and translation. Although RNA-binding proteins are critical coordinators of post-transcriptional networks, the specific RNA-binding proteins that maintain RNA homeostasis during aging remain largely unknown. Adenosine Deaminases Acting on RNA (ADARs) are conserved RNA-binding proteins that modulate lifespan across species; in humans, genetic variants in ADAR genes are enriched in centenarian populations, while in Caenorhabditis elegans, loss of the ADAR orthologs adr-1 or adr-2 significantly alters organismal lifespan. However, the precise molecular mechanisms by which ADAR proteins regulate RNA processing during aging remain unresolved. Addressing this knowledge gap is essential to determine how dysregulated RNA processing contributes to aging.
To dissect these mechanisms, I am currently focusing on the C. elegans ortholog ADR-1, which binds double-stranded regions of mRNA in young animals to maintain transcript stability, impact adenosine-to-inosine RNA editing, and regulate circular RNA (circRNA) biogenesis. Loss of adr-1 robustly shortens lifespan and upregulates specific target circRNAs, such as circ-crh-1. circRNAs are known to progressively accumulate during aging across species. Therefore, the central hypothesis of my thesis research is that ADR-1 promotes longevity by binding double-stranded regions of circRNA precursors to prevent their accumulation. Undertaking these studies is critical to understanding how the ADAR pathway influences aging and longevity.
Keywords: ADARs