| Structural highlights
Function
SHE2_YEAST RNA-binding protein that binds specific mRNAs including the ASH1 mRNA, coding for a repressor of the HO endonuclease. Part of the mRNA localization machinery that restricts accumulation of certain proteins to the bud and in the daughter cell. Recruits the MYO4-SHE3 complex to the ASH1 mRNA. Recruites also LOC1 and PUF6 to ASH1 mRNA, which are required for translational repression of this mRNA.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
Publication Abstract from PubMed
The segregation of approximately two dozen distinct mRNAs from yeast mother to daughter cell cytoplasm is a classical paradigm for eukaryotic mRNA transport. The information for transport resides in an mRNA element 40-100 nt in length, known as "zipcode." Targeted transport requires properly positioned actin filaments and cooperative loading of mRNA cargo to myosin. Cargo loading to myosin uses myosin 4 protein (Myo4p), swi5p-dependent HO expression 2 protein (She2p) and 3 protein (She3p), and zipcode. We previously determined a crystal structure of Myo4p and She3p, their 1:2 stoichiometry and interactome; we furthermore showed that the motor complex assembly requires two Myo4pShe3p heterotrimers, one She2p tetramer, and at least a single zipcode to yield a stable complex of [Myo4pShe3pShe2pzipcode] in 2:4:4:1 stoichiometry in vitro. Here, we report a structure at 2.8-A resolution of a cocrystal of a She2p tetramer bound to a segment of She3p. In this crystal structure, the She3p segment forms a striking hook that binds to a shallow hydrophobic pocket on the surface of each She2p subunit of the tetramer. Both She3p hook and cognate She2p binding pocket are composed of highly conserved residues. We also discovered a highly conserved region of She3p upstream of its hook region. Because this region consists of basic and aromatic residues, it likely represents part of She3p's binding activity for zipcode. Because She2p also exhibits zipcode-binding activity, we suggest that "hooking" She3p onto She2p aligns each of their zipcode-binding activities into a high-affinity site, thereby linking motor assembly to zipcode.
Hooking She3p onto She2p for myosin-mediated cytoplasmic mRNA transport.,Singh N, Blobel G, Shi H Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):142-7. doi: 10.1073/pnas.1423194112. , Epub 2014 Dec 22. PMID:25535369[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Munchow S, Sauter C, Jansen RP. Association of the class V myosin Myo4p with a localised messenger RNA in budding yeast depends on She proteins. J Cell Sci. 1999 May;112 ( Pt 10):1511-8. PMID:10212145
- ↑ Beach DL, Salmon ED, Bloom K. Localization and anchoring of mRNA in budding yeast. Curr Biol. 1999 Jun 3;9(11):569-78. PMID:10359695
- ↑ Bohl F, Kruse C, Frank A, Ferring D, Jansen RP. She2p, a novel RNA-binding protein tethers ASH1 mRNA to the Myo4p myosin motor via She3p. EMBO J. 2000 Oct 16;19(20):5514-24. PMID:11032818 doi:http://dx.doi.org/10.1093/emboj/19.20.5514
- ↑ Long RM, Gu W, Lorimer E, Singer RH, Chartrand P. She2p is a novel RNA-binding protein that recruits the Myo4p-She3p complex to ASH1 mRNA. EMBO J. 2000 Dec 1;19(23):6592-601. PMID:11101531 doi:http://dx.doi.org/10.1093/emboj/19.23.6592
- ↑ Kruse C, Jaedicke A, Beaudouin J, Bohl F, Ferring D, Guttler T, Ellenberg J, Jansen RP. Ribonucleoprotein-dependent localization of the yeast class V myosin Myo4p. J Cell Biol. 2002 Dec 23;159(6):971-82. Epub 2002 Dec 23. PMID:12499354 doi:http://dx.doi.org/10.1083/jcb.200207101
- ↑ Shepard KA, Gerber AP, Jambhekar A, Takizawa PA, Brown PO, Herschlag D, DeRisi JL, Vale RD. Widespread cytoplasmic mRNA transport in yeast: identification of 22 bud-localized transcripts using DNA microarray analysis. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11429-34. Epub 2003 Sep 17. PMID:13679573 doi:http://dx.doi.org/10.1073/pnas.2033246100
- ↑ Gonsalvez GB, Lehmann KA, Ho DK, Stanitsa ES, Williamson JR, Long RM. RNA-protein interactions promote asymmetric sorting of the ASH1 mRNA ribonucleoprotein complex. RNA. 2003 Nov;9(11):1383-99. PMID:14561888
- ↑ Estrada P, Kim J, Coleman J, Walker L, Dunn B, Takizawa P, Novick P, Ferro-Novick S. Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae. J Cell Biol. 2003 Dec 22;163(6):1255-66. PMID:14691136 doi:http://dx.doi.org/10.1083/jcb.200304030
- ↑ Gonsalvez GB, Little JL, Long RM. ASH1 mRNA anchoring requires reorganization of the Myo4p-She3p-She2p transport complex. J Biol Chem. 2004 Oct 29;279(44):46286-94. Epub 2004 Aug 23. PMID:15328357 doi:http://dx.doi.org/10.1074/jbc.M406086200
- ↑ Niessing D, Huttelmaier S, Zenklusen D, Singer RH, Burley SK. She2p is a novel RNA binding protein with a basic helical hairpin motif. Cell. 2004 Nov 12;119(4):491-502. PMID:15537539 doi:10.1016/j.cell.2004.10.018
- ↑ Olivier C, Poirier G, Gendron P, Boisgontier A, Major F, Chartrand P. Identification of a conserved RNA motif essential for She2p recognition and mRNA localization to the yeast bud. Mol Cell Biol. 2005 Jun;25(11):4752-66. PMID:15899876 doi:http://dx.doi.org/10.1128/MCB.25.11.4752-4766.2005
- ↑ Schmid M, Jaedicke A, Du TG, Jansen RP. Coordination of endoplasmic reticulum and mRNA localization to the yeast bud. Curr Biol. 2006 Aug 8;16(15):1538-43. PMID:16890529 doi:http://dx.doi.org/10.1016/j.cub.2006.06.025
- ↑ Du TG, Jellbauer S, Muller M, Schmid M, Niessing D, Jansen RP. Nuclear transit of the RNA-binding protein She2 is required for translational control of localized ASH1 mRNA. EMBO Rep. 2008 Aug;9(8):781-7. doi: 10.1038/embor.2008.112. Epub 2008 Jun 20. PMID:18566598 doi:http://dx.doi.org/10.1038/embor.2008.112
- ↑ Shen Z, Paquin N, Forget A, Chartrand P. Nuclear shuttling of She2p couples ASH1 mRNA localization to its translational repression by recruiting Loc1p and Puf6p. Mol Biol Cell. 2009 Apr;20(8):2265-75. doi: 10.1091/mbc.E08-11-1151. Epub 2009, Feb 25. PMID:19244342 doi:http://dx.doi.org/10.1091/mbc.E08-11-1151
- ↑ Shen Z, St-Denis A, Chartrand P. Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud. Genes Dev. 2010 Sep 1;24(17):1914-26. doi: 10.1101/gad.1937510. Epub 2010 Aug 16. PMID:20713510 doi:http://dx.doi.org/10.1101/gad.1937510
- ↑ Bertrand E, Chartrand P, Schaefer M, Shenoy SM, Singer RH, Long RM. Localization of ASH1 mRNA particles in living yeast. Mol Cell. 1998 Oct;2(4):437-45. PMID:9809065
- ↑ Singh N, Blobel G, Shi H. Hooking She3p onto She2p for myosin-mediated cytoplasmic mRNA transport. Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):142-7. doi: 10.1073/pnas.1423194112. , Epub 2014 Dec 22. PMID:25535369 doi:http://dx.doi.org/10.1073/pnas.1423194112
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