Ingmar Schaefer, Max-Planck Institute for Biochemistry
14th July 2017 at 11:00am [Download iCalendar / .ics file]
The poly(A) tail is an almost universal post-transcriptional modification present at the 3’ end of eukaryotic mRNAs. Its length is a hallmark of posttranscriptional regulation and affects the mRNAs’ nuclear export, translation and decay. The poly(A)-tail is a dynamic modification: it is added by polyadenylate polymerases and removed by deadenylases. The conserved Pan2-Pan3 deadenylase complex is recruited to poly(A) tails via the interaction with the cytoplasmic poly(A) binding protein, PABP. Here, the Pan2-Pan3 nuclease catalyzes the trimming of the poly(A) tail, which is the initial and rate limiting step of canonical eukaryotic mRNA turnover. The molecular mechanisms of the recruitment of Pan2-Pan3 to poly(A)-tails, the regulation of its deadenylase activity and the impact of this substrate-nuclease system on global cellular poly(A) distributions still remain unclear. Using cryo-EM structural approaches and biochemical assays, we are studying the substrate requirements for Pan2-Pan3. We found that poly(A)-tail length and PABP binding impact on the recruitment and activity of Pan2-Pan3. The structural and biochemical observations correlate with earlier in vivo findings of global poly(A) tail length regulation and suggest a model where Pan2-Pan3 in concert with PABP is key for maintaining steady-state poly(A)-tail length distributions in cells.
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