8c6j: Difference between revisions
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==Human spliceosomal PM5 C* complex== | |||
<StructureSection load='8c6j' size='340' side='right'caption='[[8c6j]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8c6j]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C6J FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8c6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c6j OCA], [https://pdbe.org/8c6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c6j RCSB], [https://www.ebi.ac.uk/pdbsum/8c6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c6j ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RBM22_HUMAN RBM22_HUMAN] Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.<ref>PMID:17045351</ref> <ref>PMID:21122810</ref> <ref>PMID:22246180</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Alternative precursor messenger RNA splicing is instrumental in expanding the proteome of higher eukaryotes, and changes in 3' splice site (3'ss) usage contribute to human disease. We demonstrate by small interfering RNA-mediated knockdowns, followed by RNA sequencing, that many proteins first recruited to human C* spliceosomes, which catalyze step 2 of splicing, regulate alternative splicing, including the selection of alternatively spliced NAGNAG 3'ss. Cryo-electron microscopy and protein cross-linking reveal the molecular architecture of these proteins in C* spliceosomes, providing mechanistic and structural insights into how they influence 3'ss usage. They further elucidate the path of the 3' region of the intron, allowing a structure-based model for how the C* spliceosome potentially scans for the proximal 3'ss. By combining biochemical and structural approaches with genome-wide functional analyses, our studies reveal widespread regulation of alternative 3'ss usage after step 1 of splicing and the likely mechanisms whereby C* proteins influence NAGNAG 3'ss choices. | |||
Regulation of 3' splice site selection after step 1 of splicing by spliceosomal C* proteins.,Dybkov O, Preussner M, El Ayoubi L, Feng VY, Harnisch C, Merz K, Leupold P, Yudichev P, Agafonov DE, Will CL, Girard C, Dienemann C, Urlaub H, Kastner B, Heyd F, Luhrmann R Sci Adv. 2023 Mar 3;9(9):eadf1785. doi: 10.1126/sciadv.adf1785. Epub 2023 Mar 3. PMID:36867703<ref>PMID:36867703</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8c6j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Dybkov O]] | |||
[[Category: Kastner B]] | |||
[[Category: Luehrmann R]] | |||
Revision as of 10:17, 12 July 2023
Human spliceosomal PM5 C* complexHuman spliceosomal PM5 C* complex
Structural highlights
FunctionRBM22_HUMAN Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.[1] [2] [3] Publication Abstract from PubMedAlternative precursor messenger RNA splicing is instrumental in expanding the proteome of higher eukaryotes, and changes in 3' splice site (3'ss) usage contribute to human disease. We demonstrate by small interfering RNA-mediated knockdowns, followed by RNA sequencing, that many proteins first recruited to human C* spliceosomes, which catalyze step 2 of splicing, regulate alternative splicing, including the selection of alternatively spliced NAGNAG 3'ss. Cryo-electron microscopy and protein cross-linking reveal the molecular architecture of these proteins in C* spliceosomes, providing mechanistic and structural insights into how they influence 3'ss usage. They further elucidate the path of the 3' region of the intron, allowing a structure-based model for how the C* spliceosome potentially scans for the proximal 3'ss. By combining biochemical and structural approaches with genome-wide functional analyses, our studies reveal widespread regulation of alternative 3'ss usage after step 1 of splicing and the likely mechanisms whereby C* proteins influence NAGNAG 3'ss choices. Regulation of 3' splice site selection after step 1 of splicing by spliceosomal C* proteins.,Dybkov O, Preussner M, El Ayoubi L, Feng VY, Harnisch C, Merz K, Leupold P, Yudichev P, Agafonov DE, Will CL, Girard C, Dienemann C, Urlaub H, Kastner B, Heyd F, Luhrmann R Sci Adv. 2023 Mar 3;9(9):eadf1785. doi: 10.1126/sciadv.adf1785. Epub 2023 Mar 3. PMID:36867703[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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