View source for 9fsr


==RNA Polymerase III Class III Open Mini Pre-initiation Complex 1 (OC1-mini)==
<StructureSection load='9fsr' size='340' side='right'caption='[[9fsr]], [[Resolution|resolution]] 3.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fsr]] is a 10 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=9FSR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FSR 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]] 3.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9fsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fsr OCA], [https://pdbe.org/9fsr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fsr RCSB], [https://www.ebi.ac.uk/pdbsum/9fsr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fsr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RPC1_HUMAN RPC1_HUMAN] Wiedemann-Rautenstrauch syndrome;Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome;Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome;Tremor-ataxia-central hypomyelination syndrome;Odontoleukodystrophy;Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/RPC1_HUMAN RPC1_HUMAN] Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates. Synthesizes 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci (PubMed:19609254, PubMed:19631370, PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:34675218, PubMed:35637192, PubMed:9331371). Pol III-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol III is recruited to DNA promoters type I, II or III with the help of general transcription factors and other specific initiation factors. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:33674783, PubMed:34675218). Forms Pol III active center together with the second largest subunit POLR3B/RPC2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR3A/RPC1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR3B/RPC2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate (PubMed:19609254, PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33674783, PubMed:34675218, PubMed:9331371). Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway.<ref>PMID:19609254</ref> <ref>PMID:19631370</ref> <ref>PMID:20413673</ref> <ref>PMID:33335104</ref> <ref>PMID:33558764</ref> <ref>PMID:33558766</ref> <ref>PMID:33674783</ref> <ref>PMID:34675218</ref> <ref>PMID:35637192</ref> <ref>PMID:9331371</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5). The mechanism of SNAPc cross-polymerase engagement and the role of the SNAPC2 and SNAPC5 subunits remain poorly defined. Here, we present cryo-EM structures of the full-length SNAPc-containing Pol III PIC assembled on the U6 snRNA promoter in the open and melting states at 3.2-4.2 A resolution. The structural comparison revealed differences with the Saccharomyces cerevisiae Pol III PIC and the basis of selective SNAPc engagement within Pol III and Pol II PICs. Additionally, crosslinking mass spectrometry localizes SNAPC2 and SNAPC5 near the promoter DNA, expanding upon existing descriptions of snRNA Pol III PIC structure.

Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.,Shah SZ, Perry TN, Graziadei A, Cecatiello V, Kaliyappan T, Misiaszek AD, Muller CW, Ramsay EP, Vannini A Nat Commun. 2025 Jan 2;16(1):141. doi: 10.1038/s41467-024-55553-8. PMID:39747245<ref>PMID:39747245</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fsr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cecatiello V]]
[[Category: Perry TN]]
[[Category: Ramsay EP]]
[[Category: Shah SZ]]
[[Category: Vannini A]]