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| | ==Structural basis for the assembly of the SXL-UNR translation regulatory complex== | | ==Structural basis for the assembly of the SXL-UNR translation regulatory complex== |
| - | <StructureSection load='4qqb' size='340' side='right' caption='[[4qqb]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4qqb' size='340' side='right'caption='[[4qqb]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qqb]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QQB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qqb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b7f|1b7f]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqb OCA], [https://pdbe.org/4qqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qqb RCSB], [https://www.ebi.ac.uk/pdbsum/4qqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sxl, Sx1, CG43770 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME]), Unr, CG7015, Dmel_CG7015 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqb OCA], [http://pdbe.org/4qqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qqb RCSB], [http://www.ebi.ac.uk/pdbsum/4qqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SXL_DROME SXL_DROME]] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.<ref>PMID:3144435</ref> <ref>PMID:1710769</ref> <ref>PMID:1547493</ref> | + | [https://www.uniprot.org/uniprot/SXL_DROME SXL_DROME] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.<ref>PMID:3144435</ref> <ref>PMID:1710769</ref> <ref>PMID:1547493</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Hennig, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Popowicz, G M]] | + | [[Category: Hennig J]] |
| - | [[Category: Sattler, M]] | + | [[Category: Popowicz GM]] |
| - | [[Category: Cold shock domain]] | + | [[Category: Sattler M]] |
| - | [[Category: Csd]]
| + | |
| - | [[Category: Dosage compensation]]
| + | |
| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna binding domain]]
| + | |
| - | [[Category: Rna recognition motif]]
| + | |
| - | [[Category: Rrm]]
| + | |
| - | [[Category: Tranlation-rna complex]]
| + | |
| - | [[Category: Transcription-rna complex]]
| + | |
| - | [[Category: Translation regulation]]
| + | |
| Structural highlights
Function
SXL_DROME Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.[1] [2] [3]
Publication Abstract from PubMed
Genetic equality between males and females is established by chromosome-wide dosage-compensation mechanisms. In the fruitfly Drosophila melanogaster, the dosage-compensation complex promotes twofold hypertranscription of the single male X-chromosome and is silenced in females by inhibition of the translation of msl2, which codes for the limiting component of the dosage-compensation complex. The female-specific protein Sex-lethal (Sxl) recruits Upstream-of-N-ras (Unr) to the 3' untranslated region of msl2 messenger RNA, preventing the engagement of the small ribosomal subunit. Here we report the 2.8 A crystal structure, NMR and small-angle X-ray and neutron scattering data of the ternary Sxl-Unr-msl2 ribonucleoprotein complex featuring unprecedented intertwined interactions of two Sxl RNA recognition motifs, a Unr cold-shock domain and RNA. Cooperative complex formation is associated with a 1,000-fold increase of RNA binding affinity for the Unr cold-shock domain and involves novel ternary interactions, as well as non-canonical RNA contacts by the alpha1 helix of Sxl RNA recognition motif 1. Our results suggest that repression of dosage compensation, necessary for female viability, is triggered by specific, cooperative molecular interactions that lock a ribonucleoprotein switch to regulate translation. The structure serves as a paradigm for how a combination of general and widespread RNA binding domains expands the code for specific single-stranded RNA recognition in the regulation of gene expression.
Structural basis for the assembly of the Sxl-Unr translation regulatory complex.,Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F, Sattler M Nature. 2014 Sep 7. doi: 10.1038/nature13693. PMID:25209665[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bell LR, Maine EM, Schedl P, Cline TW. Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins. Cell. 1988 Dec 23;55(6):1037-46. PMID:3144435
- ↑ Samuels ME, Schedl P, Cline TW. The complex set of late transcripts from the Drosophila sex determination gene sex-lethal encodes multiple related polypeptides. Mol Cell Biol. 1991 Jul;11(7):3584-602. PMID:1710769
- ↑ Keyes LN, Cline TW, Schedl P. The primary sex determination signal of Drosophila acts at the level of transcription. Cell. 1992 Mar 6;68(5):933-43. PMID:1547493
- ↑ Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F, Sattler M. Structural basis for the assembly of the Sxl-Unr translation regulatory complex. Nature. 2014 Sep 7. doi: 10.1038/nature13693. PMID:25209665 doi:http://dx.doi.org/10.1038/nature13693
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