Rhythmic Behavior Is Controlled by the SRm160 Splicing Factor in Drosophila melanogaster

BECKWITH, E; HERNANDO, CE; POLCOWÑUK, S; BERTOLIN, AP; MANCINI, E; CERIANI, MF; YANOVSKY, MJ

GENETICS

GENETICS SOC AM

Lugar: Bethesda; Año: 2017 vol. 207 p. 593 - 607

0016-6731

Circadian clocks organize the metabolism, physiology, and behavior of organisms throughout the day?night cycle bycontrolling daily rhythms in gene expression at the transcriptional and post-transcriptional levels. While many transcription factorsunderlying circadian oscillations are known, the splicing factors that modulate these rhythms remain largely unexplored. A genomewide assessment of the alterations of gene expression in a null mutant of the alternative splicing regulator SR-related matrix protein of160 kDa (SRm160) revealed the extent to which alternative splicing impacts on behavior-related genes. We show that SRm160 affectsgene expression in pacemaker neurons of the Drosophila brain to ensure proper oscillations of the molecular clock. A reduced level ofSRm160 in adult pacemaker neurons impairs circadian rhythms in locomotor behavior, and this phenotype is caused, at least in part, bya marked reduction in period (per) levels. Moreover, rhythmic accumulation of the neuropeptide PIGMENT DISPERSING FACTOR in thedorsal projections of these neurons is abolished after SRm160 depletion. The lack of rhythmicity in SRm160-downregulated flies isreversed by a fully spliced per construct, but not by an extra copy of the endogenous locus, showing that SRm160 positively regulatesper levels in a splicing-dependent manner. Our findings highlight the significant effect of alternative splicing on the nervous system andparticularly on brain function in an in vivo model.