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| | ==Solution structure of hnRNP G RRM in complex with the RNA 5'-AUCAAA-3'== | | ==Solution structure of hnRNP G RRM in complex with the RNA 5'-AUCAAA-3'== |
| - | <StructureSection load='2mb0' size='340' side='right' caption='[[2mb0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mb0' size='340' side='right'caption='[[2mb0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mb0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MB0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mb0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MB0 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBMX, HNRPG, RBMXP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mb0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mb0 RCSB], [http://www.ebi.ac.uk/pdbsum/2mb0 PDBsum]</span></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=2mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mb0 OCA], [https://pdbe.org/2mb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mb0 RCSB], [https://www.ebi.ac.uk/pdbsum/2mb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mb0 ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/RBMX_HUMAN RBMX_HUMAN] RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Plays also a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment.<ref>PMID:12165565</ref> <ref>PMID:12761049</ref> <ref>PMID:16707624</ref> <ref>PMID:18445477</ref> <ref>PMID:18541147</ref> <ref>PMID:19282290</ref> <ref>PMID:21327109</ref> |
| - | Regulation of SMN2 exon 7 splicing is crucial for the production of active SMN protein and the survival of Spinal Muscular Atrophy (SMA) patients. One of the most efficient activators of exon 7 inclusion is hnRNP G, which is recruited to the exon by Tra2-beta1. We report that in addition to the C-terminal region of hnRNP G, the RNA Recognition Motif (RRM) and the middle part of the protein containing the Arg-Gly-Gly (RGG) box are important for this function. To better understand the mode of action of hnRNP G in this context we determined the structure of its RRM bound to an SMN2 derived RNA. The RRM interacts with a 5'-AAN-3' motif and specifically recognizes the two consecutive adenines. By testing the effect of mutations in hnRNP G RRM and in its putative binding sites on the splicing of SMN2 exon 7, we show that it specifically binds to exon 7. This interaction is required for hnRNP G splicing activity and we propose its recruitment to a polyA tract located upstream of the Tra2-beta1 binding site. Finally, our data suggest that hnRNP G plays a major role in the recruitment of the Tra2-beta1/hnRNP G/SRSF9 trimeric complex to SMN2 exon 7.
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| - | Characterization of the RNA recognition mode of hnRNP G extends its role in SMN2 splicing regulation.,Moursy A, Allain FH, Clery A Nucleic Acids Res. 2014 Apr 4. PMID:24692659<ref>PMID:24692659</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Allain, F H.T.]] | + | [[Category: Large Structures]] |
| - | [[Category: Clery, A.]] | + | [[Category: Allain FH-T]] |
| - | [[Category: Moursy, A.]] | + | [[Category: Clery A]] |
| - | [[Category: Hnrnp g]] | + | [[Category: Moursy A]] |
| - | [[Category: Rrm]]
| + | |
| - | [[Category: Sma]]
| + | |
| - | [[Category: Smn]]
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| - | [[Category: Splicing]]
| + | |
| - | [[Category: Splicing-rna complex]]
| + | |
| Structural highlights
Function
RBMX_HUMAN RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Plays also a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Hofmann Y, Wirth B. hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1. Hum Mol Genet. 2002 Aug 15;11(17):2037-49. PMID:12165565
- ↑ Nasim MT, Chernova TK, Chowdhury HM, Yue BG, Eperon IC. HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding. Hum Mol Genet. 2003 Jun 1;12(11):1337-48. PMID:12761049
- ↑ Shin KH, Kang MK, Kim RH, Christensen R, Park NH. Heterogeneous nuclear ribonucleoprotein G shows tumor suppressive effect against oral squamous cell carcinoma cells. Clin Cancer Res. 2006 May 15;12(10):3222-8. PMID:16707624 doi:http://dx.doi.org/10.1158/1078-0432.CCR-05-2656
- ↑ Adamik B, Islam A, Rouhani FN, Hawari FI, Zhang J, Levine SJ. An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release. Biochem Biophys Res Commun. 2008 Jul 4;371(3):505-9. doi:, 10.1016/j.bbrc.2008.04.103. Epub 2008 Apr 28. PMID:18445477 doi:http://dx.doi.org/10.1016/j.bbrc.2008.04.103
- ↑ Shin KH, Kim RH, Kim RH, Kang MK, Park NH. hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip. Biochem Biophys Res Commun. 2008 Aug 8;372(4):880-5. doi:, 10.1016/j.bbrc.2008.05.175. Epub 2008 Jun 9. PMID:18541147 doi:10.1016/j.bbrc.2008.05.175
- ↑ Heinrich B, Zhang Z, Raitskin O, Hiller M, Benderska N, Hartmann AM, Bracco L, Elliott D, Ben-Ari S, Soreq H, Sperling J, Sperling R, Stamm S. Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J Biol Chem. 2009 May 22;284(21):14303-15. doi: 10.1074/jbc.M901026200. Epub 2009, Mar 12. PMID:19282290 doi:http://dx.doi.org/10.1074/jbc.M901026200
- ↑ Kanhoush R, Beenders B, Perrin C, Moreau J, Bellini M, Penrad-Mobayed M. Novel domains in the hnRNP G/RBMX protein with distinct roles in RNA binding and targeting nascent transcripts. Nucleus. 2010 Jan-Feb;1(1):109-22. doi: 10.4161/nucl.1.1.10857. PMID:21327109 doi:http://dx.doi.org/10.4161/nucl.1.1.10857
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