Poster abstracts
Poster number 89 submitted by Kiel Tietz
Pnrc2 regulates 3'UTR-mediated decay of cyclic transcripts during somitogenesis
Kiel T. Tietz (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University ), Thomas L. Gallagher (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University ), Monica C. Mannings (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University ), Zachary T. Morrow (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University ), Nicolas L. Derr (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University ), Sharon L. Amacher (Department of Molecular Genetics and Center for RNA Biology, The Ohio State University )
Abstract:
Vertebrate segmentation is regulated by the segmentation clock, a biological oscillator that controls periodic formation of embryonic segments (somites). This molecular oscillator generates cyclic gene expression in the tissue that generates somites and has the same periodicity as somite formation. Molecular components of the clock include the her/Hes family of transcriptional repressors, but additional transcripts also cycle. Maintenance of oscillatory gene expression requires that transcriptional activation and repression, RNA turnover, translation, and protein degradation are rapid (one cycle is 30 minutes in the zebrafish). Little is known about post-transcriptional control of cyclic transcripts during somitogenesis and our work employs genetic and biochemical approaches to better understand rapid cyclic transcript turnover. We have shown that loss of Proline-rich nuclear receptor coactivator 2 (Pnrc2) in zebrafish causes accumulation of cyclic transcripts like her1, deltaC, and deltaD, and that the her1 3’UTR confers instability to otherwise stable transcripts in a Pnrc2-dependent manner. To begin to identify her1 3’UTR cis-regulatory elements critical for Pnrc2-mediated decay, we show here that the last 179 nucleotides (nts) of the 725 nt her1 3’UTR is sufficient to confer rapid instability. Additionally, we show that the 3’UTR of the deltaC cyclic transcript also contains Pnrc2-mediated destabilizing elements. We have identified a Pumilio Response Element (PRE) within the last 179 nts of the her1 3’UTR that is also present in the deltaC 3’UTR and show here the PRE is necessary for the her1 3’UTR to convey rapid turnover. These results suggest Pnrc2 may function with Pumilio, a known decay factor, to regulate the rapid turnover of cyclic transcripts during somitogenesis. Our work explores mechanisms regulating oscillation dynamics during vertebrate segmentation and will further our understanding of pathways controlling post-transcriptional gene regulation.
Keywords: her1, Pumilio, Rapid mRNA turnover