The heterogeneous nuclear ribonucleoprotein Hrb87F and its possible role in the regulation of circadian rhythmicity in Drosophila melanogaster

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins with important roles in gene regulatory processes at a post-transcriptional level. They present a RNA-binding domain (RBD) or RNA recognition motif (RRM) at the N terminal of the amino acid sequence; however, the interaction with RNA is facilitated by other structural motifs including RGG repeats and double stranded RNA binding motifs (dsRBM). In Drosophila melanogaster, 14 hnRNPs are the most representative members of this RNA binding protein family, with functional and structural characteristics similar to mammalian. Among these, Hrb87F, the fly homologue of the of hnRNPA/B protein family members, was linked to the circadian rhythmicity. In the molecular machinery that generates the circadian rhythmicity, post-transcriptional mechanisms are known to have evolved to adjust and consolidate the proper pace of the clock. Although evidences of hnRNPs involvement in the circadian system are accumulating in murine models, a role of these proteins in the fly circadian system has not been demonstrated. The research described in this thesis is aimed at: -) a detailed characterization of Hrb87F, -) the identification of its potential RNA targets by using the recently developed “targets of RNA-binding proteins identified by editing” (TRIBE) technique, -) a behavioral analysis of the circadian rhythmicity of flies in which Hrb87F is downregulated.