Poster abstracts
Poster number 133 submitted by Kiel Tietz
Rapid clearance of oscillating transcripts during somitogenesis requires the decay adapter Pnrc2
Kiel T. Tietz (Department of Molecular Genetics, The Ohio State University), Thomas L. Gallagher, Nicolas L. Derr (Department of Molecular Genetics, The Ohio State University), Courtney E. French (Department of Plant and Microbial Biology, University of California, Berkeley), Jasmine M. McCammon (Department of Molecular and Cell Biology, University of California, Berkeley), Steven E. Brenner (Department of Molecular and Cell Biology, University of California, Berkeley), Sharon L. Amacher (Department of Molecular Genetics, The Ohio State University)
Abstract:
Vertebrate segmentation is controlled by the segmentation clock, a biological oscillator that controls periodic formation of embryonic segments, or somites. This molecular oscillator generates cyclic gene expression in the presomitic mesoderm (PSM) and has the same periodicity as that of somite formation. Core cyclic components of the segmentation clock include the hes/her family of transcriptional repressors, but additional transcripts also cycle. Maintenance of the oscillation period requires that transcriptional activation and repression, RNA turnover, translation, and protein degradation are all very rapid as somite pairs quickly develop in all vertebrates, just 30 minutes in the zebrafish model. Our lab isolated a zebrafish segmentation clock mutant, tortugab644; mutant embryos express elevated levels of cyclic mRNAs such as her1 and rhov. We have demonstrated that loss of Proline-rich nuclear receptor coactivator protein Pnrc2 is responsible for cyclic transcript accumulation in tortugab644 mutants. In human cell culture systems, Pnrc2 has been implicated in mRNA decay through interactions with Dcp1a and Upf1. Data from our lab supports a similar mRNA decay function in zebrafish since partial depletion of both Pnrc2 and Upf1 increases her1 and rhov accumulation.
We hypothesize that in pnrc2 mutants, oscillating transcripts accumulate due to inefficient removal of the 5’ cap, thus causing mRNA perdurance. In order to test this hypothesis, we are examining if Pnrc2 regulates the localization, decapping, or deadenylation of her1 and rhov transcripts and if these accumulating transcripts are actively being translated. While the mechanisms of aberrant mRNA decay are well studied, less is understood about pathways regulating decay of non-aberrant transcripts. Our goal is to define mechanisms critical for the rapid turnover of oscillating genes during somitogenesis.
Keywords: Pnrc2, her1 , rhov