Structural highlights
Function
PAN2_CHATD Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein PAB1. PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails.[HAMAP-Rule:MF_03182][1]
Publication Abstract from PubMed
The PAN2-PAN3 complex functions in general and microRNA-mediated mRNA deadenylation. However, mechanistic insight into PAN2 and its complex with the asymmetric PAN3 dimer is lacking. Here, we describe crystal structures that show that Neurospora crassa PAN2 comprises two independent structural units: a C-terminal catalytic unit and an N-terminal assembly unit that engages in a bipartite interaction with PAN3 dimers. The catalytic unit contains the exonuclease domain in an intimate complex with a potentially modulatory ubiquitin-protease-like domain. The assembly unit contains a WD40 propeller connected to an adaptable linker. The propeller contacts the PAN3 C-terminal domain, whereas the linker reinforces the asymmetry of the PAN3 dimer and prevents the recruitment of a second PAN2 molecule. Functional data indicate an essential role for PAN3 in coordinating PAN2-mediated deadenylation with subsequent steps in mRNA decay, which lead to complete mRNA degradation.
An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay.,Jonas S, Christie M, Peter D, Bhandari D, Loh B, Huntzinger E, Weichenrieder O, Izaurralde E Nat Struct Mol Biol. 2014 Jun 1. doi: 10.1038/nsmb.2837. PMID:24880343[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wolf J, Valkov E, Allen MD, Meineke B, Gordiyenko Y, McLaughlin SH, Olsen TM, Robinson CV, Bycroft M, Stewart M, Passmore LA. Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation. EMBO J. 2014 May 28. pii: e201488373. PMID:24872509 doi:http://dx.doi.org/10.15252/embj.201488373
- ↑ Jonas S, Christie M, Peter D, Bhandari D, Loh B, Huntzinger E, Weichenrieder O, Izaurralde E. An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay. Nat Struct Mol Biol. 2014 Jun 1. doi: 10.1038/nsmb.2837. PMID:24880343 doi:http://dx.doi.org/10.1038/nsmb.2837
