6tr0

From Proteopedia

(Difference between revisions)

Revision as of 11:03, 14 June 2023

Solution structure of U2AF2 RRM1,2

Structural highlights

6tr0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

U2AF2_HUMAN Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The recognition of cis-regulatory RNA motifs in human transcripts by RNA binding proteins (RBPs) is essential for gene regulation. The molecular features that determine RBP specificity are often poorly understood. Here, we combined NMR structural biology with high-throughput iCLIP approaches to identify a regulatory mechanism for U2AF2 RNA recognition. We found that the intrinsically disordered linker region connecting the two RNA recognition motif (RRM) domains of U2AF2 mediates autoinhibitory intramolecular interactions to reduce nonproductive binding to weak Py-tract RNAs. This proofreading favors binding of U2AF2 at stronger Py-tracts, as required to define 3' splice sites at early stages of spliceosome assembly. Mutations that impair the linker autoinhibition enhance the affinity for weak Py-tracts result in promiscuous binding of U2AF2 along mRNAs and impact on splicing fidelity. Our findings highlight an important role of intrinsically disordered linkers to modulate RNA interactions of multidomain RBPs.

An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2.,Kang HS, Sanchez-Rico C, Ebersberger S, Sutandy FXR, Busch A, Welte T, Stehle R, Hipp C, Schulz L, Buchbender A, Zarnack K, Konig J, Sattler M Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7140-7149. doi:, 10.1073/pnas.1913483117. Epub 2020 Mar 18. PMID:32188783^[4]

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

References

↑ Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664
↑ Warf MB, Diegel JV, von Hippel PH, Berglund JA. The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9203-8. doi:, 10.1073/pnas.0900342106. Epub 2009 May 26. PMID:19470458 doi:10.1073/pnas.0900342106
↑ Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Bottger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3. PMID:19574390 doi:325/5936/90
↑ Kang HS, Sánchez-Rico C, Ebersberger S, Sutandy FXR, Busch A, Welte T, Stehle R, Hipp C, Schulz L, Buchbender A, Zarnack K, König J, Sattler M. An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7140-7149. PMID:32188783 doi:10.1073/pnas.1913483117

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6tr0"

Categories: Homo sapiens | Large Structures | Kang H-S | Sattler M

@@ Line 3: / Line 3: @@
 <StructureSection load='6tr0' size='340' side='right'caption='[[6tr0]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TR0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TR0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tr0]] is a 1 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=6TR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TR0 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tr0 OCA], [http://pdbe.org/6tr0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tr0 RCSB], [http://www.ebi.ac.uk/pdbsum/6tr0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tr0 ProSAT]</span></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=6tr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tr0 OCA], [https://pdbe.org/6tr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tr0 RCSB], [https://www.ebi.ac.uk/pdbsum/6tr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tr0 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/U2AF2_HUMAN U2AF2_HUMAN] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:15009664</ref> <ref>PMID:19470458</ref> <ref>PMID:19574390</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The recognition of cis-regulatory RNA motifs in human transcripts by RNA binding proteins (RBPs) is essential for gene regulation. The molecular features that determine RBP specificity are often poorly understood. Here, we combined NMR structural biology with high-throughput iCLIP approaches to identify a regulatory mechanism for U2AF2 RNA recognition. We found that the intrinsically disordered linker region connecting the two RNA recognition motif (RRM) domains of U2AF2 mediates autoinhibitory intramolecular interactions to reduce nonproductive binding to weak Py-tract RNAs. This proofreading favors binding of U2AF2 at stronger Py-tracts, as required to define 3' splice sites at early stages of spliceosome assembly. Mutations that impair the linker autoinhibition enhance the affinity for weak Py-tracts result in promiscuous binding of U2AF2 along mRNAs and impact on splicing fidelity. Our findings highlight an important role of intrinsically disordered linkers to modulate RNA interactions of multidomain RBPs.
+An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2.,Kang HS, Sanchez-Rico C, Ebersberger S, Sutandy FXR, Busch A, Welte T, Stehle R, Hipp C, Schulz L, Buchbender A, Zarnack K, Konig J, Sattler M Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7140-7149. doi:, 10.1073/pnas.1913483117. Epub 2020 Mar 18. PMID:32188783<ref>PMID:32188783</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6tr0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Kang H-S]]
 [[Category: Sattler M]]

6tr0

From Proteopedia

Revision as of 11:03, 14 June 2023

Solution structure of U2AF2 RRM1,2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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