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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 21 599-608 (2014)
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Cited: 30 times
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Abstract

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.

Reviews citing this publication (11)

  1. Towards a molecular understanding of microRNA-mediated gene silencing. Jonas S, Izaurralde E. Nat Rev Genet 16 421-433 (2015)
  2. The Functions of MicroRNAs: mRNA Decay and Translational Repression. Iwakawa HO, Tomari Y. Trends Cell Biol 25 651-665 (2015)
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  1. Phase Transitions in the Assembly and Function of Human miRISC. Sheu-Gruttadauria J, MacRae IJ. Cell 173 946-957.e16 (2018)
  2. Regulation of gene expression in trypanosomatids: living with polycistronic transcription. Clayton C. Open Biol 9 190072 (2019)
  3. Molecular Basis for poly(A) RNP Architecture and Recognition by the Pan2-Pan3 Deadenylase. Schäfer IB, Yamashita M, Schuller JM, Schüssler S, Reichelt P, Strauss M, Conti E. Cell 177 1619-1631.e21 (2019)
  4. Progressive Hearing Loss in Mice Carrying a Mutation in Usp53. Kazmierczak M, Harris SL, Kazmierczak P, Shah P, Starovoytov V, Ohlemiller KK, Schwander M. J Neurosci 35 15582-15598 (2015)
  5. The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases. Tang TTL, Stowell JAW, Hill CH, Passmore LA. Nat Struct Mol Biol 26 433-442 (2019)
  6. Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association. Patel O, Griffin MDW, Panjikar S, Dai W, Ma X, Chan H, Zheng C, Kropp A, Murphy JM, Daly RJ, Lucet IS. Nat Commun 8 1157 (2017)
  7. USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization. Yang S, Liu L, Cao C, Song N, Wang Y, Ma S, Zhang Q, Yu N, Ding X, Yang F, Tian S, Zhang K, Sun T, Yang J, Yao Z, Wu S, Shi L. Nat Commun 9 1285 (2018)
  8. Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex. Chen Y, Khazina E, Izaurralde E, Weichenrieder O. Nucleic Acids Res 49 6489-6510 (2021)
  9. Recognition of Poly(A) RNA through Its Intrinsic Helical Structure. Tang TTL, Passmore LA. Cold Spring Harb Symp Quant Biol 84 21-30 (2019)
  10. Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1. Chen J, Liu L, You C, Gu J, Ruan W, Zhang L, Gan J, Cao C, Huang Y, Chen X, Ma J. Nat Commun 9 3585 (2018)
  11. ECOD: identification of distant homology among multidomain and transmembrane domain proteins. Schaeffer RD, Kinch L, Medvedev KE, Pei J, Cheng H, Grishin N. BMC Mol Cell Biol 20 18 (2019)
  12. Antagonistic actions of two human Pan3 isoforms on global mRNA turnover. Chen CA, Zhang Y, Xiang Y, Han L, Chang JT, Shyu AB. RNA 23 1404-1418 (2017)
  13. CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis. Zeng J, Zhang Z, Liao Q, Lu Q, Liu J, Yuan L, Liu G. Front Cell Dev Biol 9 719898 (2021)
  14. Case Reports PAN3-PSMA2 fusion resulting from a novel t(7;13)(p14;q12) chromosome translocation in a myelodysplastic syndrome that evolved into acute myeloid leukemia. Panagopoulos I, Gorunova L, Andersen HK, Bergrem A, Dahm A, Andersen K, Micci F, Heim S. Exp Hematol Oncol 7 7 (2018)
  15. Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets. Shin JJ, Aftab Q, Austin P, McQueen JA, Poon T, Li SC, Young BP, Roskelley CD, Loewen CJ. Dis Model Mech 9 1039-1049 (2016)
  16. Deadenylation-a piece of PANcake. Stubbs MT, Wahle E. EMBO J 33 1503-1505 (2014)
  17. Identification and classification of papain-like cysteine proteinases. Ozhelvaci F, Steczkiewicz K. J Biol Chem 299 104801 (2023)
  18. PAN-orama: three convergent views of a eukaryotic deadenylase. Martin S, Coller J. Nat Struct Mol Biol 21 577-578 (2014)
  19. The Dynamic Poly(A) Tail Acts as a Signal Hub in mRNA Metabolism. Zhang G, Luo H, Li X, Hu Z, Wang Q. Cells 12 572 (2023)


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