Aarhus Universitets segl

MBG Focus Talk: Physiological and Molecular functions of circRNAs

Sebastian Kadener, Department of Biology, Brandeis University

Oplysninger om arrangementet

Tidspunkt

Mandag 9. oktober 2023,  kl. 15:15 - 16:00

Sted

Faculty Club (1870-816)

Circular RNAs (circRNAs) are abundant RNAs of largely unknown function. To uncover circRNA function we performed a genetic screen using Drosophila and generated >100 different fly strains, which express shRNAs against circRNAs that are highly expressed in fly heads. Constitutive expression of most of them (>90%) resulted in a specific and strong reduction (85-100%) of the targeted circRNAs. We performed a comprehensive assessment of these strains including: 1. Developmental delay and lethality; 2. Gene expression by RNAseq in the brain of in young and aged flies; 3. Behavioral assessment including locomotor activity, food preference, climbing and fertility and 4. Lifespan. Interestingly, we found that knockdown of specific circRNAs provoke very different effects on the transcriptome as well as specific behavioral defects, which we are now studying at the mechanistic level.  Moreover, we identify a subset of circRNAs that extend lifespan when downregulated. Interestingly, these long-lived flies displayed “younger” transcriptomes with altered expression of several known lifespan regulators. We also generated a comprehensive RNAseq profile of fly heads across age and found that circRNAs can be used to determine age with much higher precision than mRNAs.. Together, our results constitute the first global assessment of circRNA functionality at the organismal level.