Abstract
In animal oocytes and early embryos, mRNA poly(A)-tail length strongly influences translational efficiency (TE), but later in development this coupling between tail length and TE disappears. Here, we elucidate how this coupling is first established and why it disappears. Overexpressing cytoplasmic poly(A)-binding protein (PABPC) in Xenopus oocytes specifically improved translation of short-tailed mRNAs, thereby diminishing coupling between tail length and TE. Thus, strong coupling requires limiting PABPC, implying that in coupled systems longer-tail mRNAs better compete for limiting PABPC. In addition to expressing excess PABPC, post-embryonic mammalian cell lines had two other properties that prevented strong coupling: terminal-uridylation-dependent destabilization of mRNAs lacking bound PABPC, and a regulatory regime wherein PABPC contributes minimally to TE. Thus, these results revealed three fundamental mechanistic requirements for coupling and defined the context-dependent functions for PABPC, which promotes TE but not mRNA stability in coupled systems and mRNA stability but not TE in uncoupled systems.
Highlights
Most eukaryotic mRNAs are polyadenylated at their 30 ends in a process associated with transcriptional termination
Limiting PABPC is required for tail length to strongly influence translational efficiency (TE) of reporter mRNAs
To assay the influence of poly(A)-tail length on TE, we used an in vitro translation extract made from stage VI Xenopus laevis oocytes, where cytoplasmic polyadenylation leads to translational activation of the c-mos, cdk2 and some cyclin mRNAs (Richter and Lasko, 2011)
Summary
Most eukaryotic mRNAs are polyadenylated at their 30 ends in a process associated with transcriptional termination. Pioneering studies in maturing oocytes and early embryos show that lengthening of poly(A) tails through cytoplasmic polyadenylation is critical for regulating gene expression during these early stages of animal development (Richter, 1999; Salles et al, 1994; Sheets et al, 1995). Both unfertilized eggs and early-stage embryos lack the ability to create or destroy mRNAs, and cannot adjust the number of mRNA molecules available for translation These cells can only regulate how efficiently each mRNA is translated. Xiang and Bartel studied frog eggs, and discovered that artificially raising levels of a protein that binds poly(A) tails, known as PABPC, improved the translation of shorttailed mRNAs to create a situation in which both short- and long-tailed mRNAs were translated with near-equal efficiency. We uncover mechanistic requirements for coupling between poly(A)-tail length and TE observed in oocytes and early embryos, showing that this coupling and the subsequent uncoupling observed later in development rely on a context-dependent switch in the function of PABPCs
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