5mpl

From Proteopedia

(Difference between revisions)

Revision as of 06:31, 16 November 2017

hnRNP A1 RRM2 in complex with 5'-UCAGUU-3' RNA

Structural highlights

5mpl is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5mpg
Gene:	HNRNPA1, HNRPA1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ROA1_HUMAN] Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.^[1] The disease is caused by mutations affecting the gene represented in this entry.^[2]

Function

[ROA1_HUMAN] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.^[3]

Publication Abstract from PubMed

HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function. The disruption of the inter-RRM interaction or the loss of RNA binding capacity of either RRM impairs splicing repression by hnRNP A1. Furthermore, both binding sites within the ISS-N1 are important for splicing repression and their contributions are cumulative rather than synergistic.

Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7.,Beusch I, Barraud P, Moursy A, Clery A, Allain FH Elife. 2017 Jun 26;6. pii: e25736. doi: 10.7554/eLife.25736. PMID:28650318^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
↑ Kim CS, Seol SK, Song OK, Park JH, Jang SK. An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. J Virol. 2007 Apr;81(8):3852-65. Epub 2007 Jan 17. PMID:17229681 doi:http://dx.doi.org/10.1128/JVI.01311-06
↑ Beusch I, Barraud P, Moursy A, Clery A, Allain FH. Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7. Elife. 2017 Jun 26;6. pii: e25736. doi: 10.7554/eLife.25736. PMID:28650318 doi:http://dx.doi.org/10.7554/eLife.25736

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mpl"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5mpl is ON HOLD  until Paper Publication
+==hnRNP A1 RRM2 in complex with 5'-UCAGUU-3' RNA==
+<StructureSection load='5mpl' size='340' side='right' caption='[[5mpl]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5mpl]] 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=5MPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MPL FirstGlance]. <br>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5mpg|5mpg]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNRNPA1, HNRPA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5mpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mpl OCA], [http://pdbe.org/5mpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mpl RCSB], [http://www.ebi.ac.uk/pdbsum/5mpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mpl ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref>   The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.<ref>PMID:17229681</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function. The disruption of the inter-RRM interaction or the loss of RNA binding capacity of either RRM impairs splicing repression by hnRNP A1. Furthermore, both binding sites within the ISS-N1 are important for splicing repression and their contributions are cumulative rather than synergistic.
-Authors:
+Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7.,Beusch I, Barraud P, Moursy A, Clery A, Allain FH Elife. 2017 Jun 26;6. pii: e25736. doi: 10.7554/eLife.25736. PMID:28650318<ref>PMID:28650318</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5mpl" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Allain, F H.T]]
+[[Category: Barraud, P]]
+[[Category: Hnrnp]]
+[[Category: Rna]]
+[[Category: Rrm]]
+[[Category: Splicing]]

5mpl

From Proteopedia

Revision as of 06:31, 16 November 2017

hnRNP A1 RRM2 in complex with 5'-UCAGUU-3' RNA

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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