Oral Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Recruiting the PAN2-PAN3 complex to miRNA targets (#8)

Mary Christie 1 2 3 , Stephanie Jonas 2 , Andreas Boland 2 , Daniel Peter 2 , Eric Huntzinger 2 , Dipankar Bhandari 2 , Belinda Loh 2 , Oliver Weichenrieder 2 , Elisa Izaurralde 2
  1. Faculty of Medicine, St Vincent's Clinical School, The University of New South Wales, Sydney
  2. Max Planck Institute for Developmental Biology, Tuebingen
  3. Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia

mRNA degradation is an essential component of the gene expression process. Cytoplasmic mRNA decay is typically initiated by the removal of poly(A) tails, a process termed deadenylation, which causes translational repression and, in most cases, triggers irreversible mRNA degradation. The PAN2-PAN3 deadenylase complex functions in both bulk and microRNA-mediated mRNA decay and is directly recruited to miRNA targets by GW182/ TNRC6 proteins. Taking a structural and functional approach, we have identified unusual features that mediate the interaction of PAN3 with PAN2 and TNRC6 proteins, as well as critical residues required for mRNA degradation in vivo 1,2. Collectively, our data describes the structural basis for the recruitment of the PAN2-PAN3 complex to miRNA targets by TNRC6 proteins, and the essential role of PAN3 in coordinating deadenylation with downstream steps of the mRNA decay pathway.

References

1) Christie, M*., Boland, A*., Huntzinger, E., Weichenrieder, O., Izaurralde, E. (2013). Molecular Cell, 51(3): 360-373

2) Jonas, S*., Christie, M*., Peter, D., Bhandari, D., Loh, B., Huntzinger, E., Weichenrieder, O., Izaurralde, E. (2014). Nature Structural and Molecular Biology 21:599-608