Poster abstracts

Poster number 21 submitted by Sarah Geisler

Evidence for feedback between mRNA destruction and mRNA biogenesis

Sarah Geisler (Center for RNA Molecular Biology, School of Medicine, Case Western Reserve University), Jeff Coller (Center for RNA Molecular Biology, School of Medicine, Case Western Reserve University)

Abstract:
The level of steady-state mRNA in the cell is a representation of the amount of mRNA synthesized by transcription minus the amount destroyed by the turnover pathway. In this study we provide evidence that mRNA decay rates can directly impact new mRNA synthesis. Eukaryotic mRNA turnover is initiated by the loss of the poly(A) tail, followed by decapping, and subsequent 5’-3’ exoribonuclease digestion. Mutations that block mRNA decapping result in dramatic stabilization of the mRNA in a transcriptional pulse-chase experiment. Shockingly, however, while the mRNA is five-fold more stable when decapping is impaired, there is no excess mRNA accumulation at steady state relative to WT. The incongruence between stabilization and steady-state levels is observed on multiple mRNAs, suggesting a widespread phenomenon. Moreover, while decapping mutants effect a step subsequent to deadenylation, the reduction in mRNA observed is on polyadenylated messages; implying an affect on newly generated transcripts. In addition, the impact on steady-state is specific to the decapping step and not seen when exonucleolytic digestion of the message is impaired. Our preliminary data suggests that this phenomena is a result of specific feedback between mRNA decapping and new mRNA transcription. This raises the possibility of a novel feedback loop, or retrocoupling event in which the proper destruction of the mRNA is required for the new generation of mRNA transcripts. Moreover, these findings demonstrate that the absolute levels of mRNA within the cell are kept at a finely controlled balance by both synthesis and destruction.

Keywords: mRNA decay, mRNA decapping, mRNA biogenesis