| Structural highlights
Function
SKI2_YEAST RNA helicase component of the SKI complex involved in 3'-mRNA degradation pathway. Represses dsRNA virus propagation by specifically blocking translation of viral mRNAs, perhaps recognizing the absence of CAP or poly(A). Essential for cell growth only in the presence of M1 replicon.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
Publication Abstract from PubMed
The Ski2-Ski3-Ski8 (Ski238) helicase complex directs cytoplasmic mRNAs toward the nucleolytic exosome complex for degradation. In yeast, the interaction between Ski238 and exosome requires the adaptor protein Ski7. We determined different cryo-EM structures of the Ski238 complex depicting the transition from a rigid autoinhibited closed conformation to a flexible active open conformation in which the Ski2 helicase module has detached from the rest of Ski238. The open conformation favors the interaction of the Ski3 subunit with exosome-bound Ski7, leading to the recruitment of the exosome. In the Ski238-Ski7-exosome holocomplex, the Ski2 helicase module binds the exosome cap, enabling the RNA to traverse from the helicase through the internal exosome channel to the Rrp44 exoribonuclease. Our study pinpoints how conformational changes within the Ski238 complex regulate exosome recruitment for RNA degradation. We also reveal the remarkable conservation of helicase-exosome RNA channeling mechanisms throughout eukaryotic nuclear and cytoplasmic exosome complexes.
Concerted structural rearrangements enable RNA channeling into the cytoplasmic Ski238-Ski7-exosome assembly.,Keidel A, Kogel A, Reichelt P, Kowalinski E, Schafer IB, Conti E Mol Cell. 2023 Oct 19:S1097-2765(23)00803-1. doi: 10.1016/j.molcel.2023.09.037. PMID:37879335[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Widner WR, Wickner RB. Evidence that the SKI antiviral system of Saccharomyces cerevisiae acts by blocking expression of viral mRNA. Mol Cell Biol. 1993 Jul;13(7):4331-41. PMID:8321235
- ↑ Toh-E A, Guerry P, Wickner RB. Chromosomal superkiller mutants of Saccharomyces cerevisiae. J Bacteriol. 1978 Dec;136(3):1002-7. PMID:363683
- ↑ Ridley SP, Sommer SS, Wickner RB. Superkiller mutations in Saccharomyces cerevisiae suppress exclusion of M2 double-stranded RNA by L-A-HN and confer cold sensitivity in the presence of M and L-A-HN. Mol Cell Biol. 1984 Apr;4(4):761-70. PMID:6371496
- ↑ Johnson AW, Kolodner RD. Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of Saccharomyces cerevisiae is independent of killer virus and suggests a general role for these genes in translation control. Mol Cell Biol. 1995 May;15(5):2719-27. PMID:7739552
- ↑ Masison DC, Blanc A, Ribas JC, Carroll K, Sonenberg N, Wickner RB. Decoying the cap- mRNA degradation system by a double-stranded RNA virus and poly(A)- mRNA surveillance by a yeast antiviral system. Mol Cell Biol. 1995 May;15(5):2763-71. PMID:7739557
- ↑ Anderson JS, Parker RP. The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex. EMBO J. 1998 Mar 2;17(5):1497-506. PMID:9482746 doi:10.1093/emboj/17.5.1497
- ↑ van Hoof A, Lennertz P, Parker R. Yeast exosome mutants accumulate 3'-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol Cell Biol. 2000 Jan;20(2):441-52. PMID:10611222
- ↑ Brown JT, Bai X, Johnson AW. The yeast antiviral proteins Ski2p, Ski3p, and Ski8p exist as a complex in vivo. RNA. 2000 Mar;6(3):449-57. PMID:10744028
- ↑ Searfoss AM, Wickner RB. 3' poly(A) is dispensable for translation. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9133-7. PMID:10922069
- ↑ Araki Y, Takahashi S, Kobayashi T, Kajiho H, Hoshino S, Katada T. Ski7p G protein interacts with the exosome and the Ski complex for 3'-to-5' mRNA decay in yeast. EMBO J. 2001 Sep 3;20(17):4684-93. PMID:11532933 doi:10.1093/emboj/20.17.4684
- ↑ Brown JT, Johnson AW. A cis-acting element known to block 3' mRNA degradation enhances expression of polyA-minus mRNA in wild-type yeast cells and phenocopies a ski mutant. RNA. 2001 Nov;7(11):1566-77. PMID:11720286
- ↑ Mitchell P, Tollervey D. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'-->5' degradation. Mol Cell. 2003 May;11(5):1405-13. PMID:12769863
- ↑ Kushner DB, Lindenbach BD, Grdzelishvili VZ, Noueiry AO, Paul SM, Ahlquist P. Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15764-9. Epub 2003 Dec 11. PMID:14671320 doi:10.1073/pnas.2536857100
- ↑ Keidel A, Kögel A, Reichelt P, Kowalinski E, Schäfer IB, Conti E. Concerted structural rearrangements enable RNA channeling into the cytoplasmic Ski238-Ski7-exosome assembly. Mol Cell. 2023 Oct 19:S1097-2765(23)00803-1. PMID:37879335 doi:10.1016/j.molcel.2023.09.037
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