| Structural highlights
Function
[SUB2_YEAST] ATP-binding RNA helicase component of the TREX complex involved in transcription elongation and required for the export of mRNA out of the nucleus. SUB2 plays also a role in pre-mRNA splicing and spliceosome assembly. May be involved in rDNA and telomeric silencing, and maintenance of genome integrity.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
Publication Abstract from PubMed
mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6.0 A resolution; and Sub2 associated with an ATP analogue, RNA, and a C-terminal fragment of Yra1 (Yra1-C) at 2.6 A resolution. We found that the 25 nm long THO clamps Sub2 in a half-open configuration; in contrast, when bound to the ATP analogue, RNA and Yra1-C, Sub2 assumes a closed conformation. Both THO and Yra1-C stimulated Sub2's intrinsic ATPase activity. We propose that THO surveys common landmarks in each nuclear mRNP to localize Sub2 for targeted loading of Yra1.
Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1.,Ren Y, Schmiege P, Blobel G Elife. 2017 Jan 6;6. pii: e20070. doi: 10.7554/eLife.20070. PMID:28059701[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shiratori A, Shibata T, Arisawa M, Hanaoka F, Murakami Y, Eki T. Systematic identification, classification, and characterization of the open reading frames which encode novel helicase-related proteins in Saccharomyces cerevisiae by gene disruption and Northern analysis. Yeast. 1999 Feb;15(3):219-53. PMID:10077188 doi:<219::AID-YEA349>3.0.CO;2-3 https://dx.doi.org/10.1002/(SICI)1097-0061(199902)15:3<219::AID-YEA349>3.0.CO;2-3
- ↑ Zhang M, Green MR. Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. Genes Dev. 2001 Jan 1;15(1):30-5. PMID:11156602
- ↑ Libri D, Graziani N, Saguez C, Boulay J. Multiple roles for the yeast SUB2/yUAP56 gene in splicing. Genes Dev. 2001 Jan 1;15(1):36-41. PMID:11156603
- ↑ Kistler AL, Guthrie C. Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. Genes Dev. 2001 Jan 1;15(1):42-9. PMID:11156604
- ↑ Fan HY, Merker RJ, Klein HL. High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Mol Cell Biol. 2001 Aug;21(16):5459-70. PMID:11463828 doi:https://dx.doi.org/10.1128/MCB.21.16.5459-5470.2001
- ↑ Strasser K, Hurt E. Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p. Nature. 2001 Oct 11;413(6856):648-52. PMID:11675790 doi:https://dx.doi.org/10.1038/35098113
- ↑ Jensen TH, Boulay J, Rosbash M, Libri D. The DECD box putative ATPase Sub2p is an early mRNA export factor. Curr Biol. 2001 Oct 30;11(21):1711-5. PMID:11696331
- ↑ Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002 May 16;417(6886):304-8. Epub 2002 Apr 28. PMID:11979277 doi:https://dx.doi.org/10.1038/nature746
- ↑ West RW Jr, Milgrom E. DEAD-box RNA helicase Sub2 is required for expression of lacZ fusions in Saccharomyces cerevisiae and is a dosage-dependent suppressor of RLR1 (THO2). Gene. 2002 Apr 17;288(1-2):19-27. PMID:12034490
- ↑ Jimeno S, Rondon AG, Luna R, Aguilera A. The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J. 2002 Jul 1;21(13):3526-35. PMID:12093753 doi:https://dx.doi.org/10.1093/emboj/cdf335
- ↑ Zenklusen D, Vinciguerra P, Wyss JC, Stutz F. Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p. Mol Cell Biol. 2002 Dec;22(23):8241-53. PMID:12417727
- ↑ Rondon AG, Jimeno S, Garcia-Rubio M, Aguilera A. Molecular evidence that the eukaryotic THO/TREX complex is required for efficient transcription elongation. J Biol Chem. 2003 Oct 3;278(40):39037-43. Epub 2003 Jul 18. PMID:12871933 doi:https://dx.doi.org/10.1074/jbc.M305718200
- ↑ Lahue E, Heckathorn J, Meyer Z, Smith J, Wolfe C. The Saccharomyces cerevisiae Sub2 protein suppresses heterochromatic silencing at telomeres and subtelomeric genes. Yeast. 2005 May;22(7):537-51. PMID:15942929 doi:https://dx.doi.org/10.1002/yea.1231
- ↑ Ren Y, Schmiege P, Blobel G. Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1. Elife. 2017 Jan 6;6. pii: e20070. doi: 10.7554/eLife.20070. PMID:28059701 doi:https://dx.doi.org/10.7554/eLife.20070
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