9fss

RNA Polymerase III Class III Open Mini Pre-Initiation complex 2 (OC2-mini)

Structural highlights

9fss is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.14Å
Ligands:	MG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RPC4_HUMAN DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:12391170, PubMed:20413673, PubMed:33558764, PubMed:34675218, PubMed:35637192). Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Assembles with POLR3E/RPC5 forming a subcomplex that binds the Pol III core. Enables recruitment of Pol III at transcription initiation site and drives transcription initiation from both type 2 and type 3 DNA promoters. Required for efficient transcription termination and reinitiation (By similarity) (PubMed:12391170, PubMed:20413673, PubMed:35637192). Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as 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 (PubMed:19609254, PubMed:19631370).[UniProtKB:P25441]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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^[8]

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

References

↑ Hu P, Wu S, Sun Y, Yuan CC, Kobayashi R, Myers MP, Hernandez N. Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits. Mol Cell Biol. 2002 Nov;22(22):8044-55. PMID:12391170 doi:10.1128/MCB.22.22.8044-8055.2002
↑ Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009 Oct;10(10):1065-72. doi: 10.1038/ni.1779. Epub 2009 Jul 16. PMID:19609254 doi:10.1038/ni.1779
↑ Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009 Aug 7;138(3):576-91. doi: 10.1016/j.cell.2009.06.015. Epub 2009 Jul, 23. PMID:19631370 doi:10.1016/j.cell.2009.06.015
↑ Canella D, Praz V, Reina JH, Cousin P, Hernandez N. Defining the RNA polymerase III transcriptome: Genome-wide localization of the RNA polymerase III transcription machinery in human cells. Genome Res. 2010 Jun;20(6):710-21. PMID:20413673 doi:10.1101/gr.101337.109
↑ Girbig M, Misiaszek AD, Vorländer MK, Lafita A, Grötsch H, Baudin F, Bateman A, Müller CW. Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states. Nat Struct Mol Biol. 2021 Feb;28(2):210-219. PMID:33558764 doi:10.1038/s41594-020-00555-5
↑ Hou H, Li Y, Wang M, Liu A, Yu Z, Chen K, Zhao D, Xu Y. Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine. Nat Commun. 2021 Oct 21;12(1):6135. PMID:34675218 doi:10.1038/s41467-021-26402-9
↑ Van Bortle K, Marciano DP, Liu Q, Chou T, Lipchik AM, Gollapudi S, Geller BS, Monte E, Kamakaka RT, Snyder MP. A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA. Nat Commun. 2022 May 30;13(1):3007. PMID:35637192 doi:10.1038/s41467-022-30323-6
↑ Shah SZ, Perry TN, Graziadei A, Cecatiello V, Kaliyappan T, Misiaszek AD, Müller CW, Ramsay EP, Vannini A. Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters. Nat Commun. 2025 Jan 2;16(1):141. PMID:39747245 doi:10.1038/s41467-024-55553-8

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OCA

[1] Hu P, Wu S, Sun Y, Yuan CC, Kobayashi R, Myers MP, Hernandez N. Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits. Mol Cell Biol. 2002 Nov;22(22):8044-55. PMID:12391170 doi:10.1128/MCB.22.22.8044-8055.2002

[2] Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009 Oct;10(10):1065-72. doi: 10.1038/ni.1779. Epub 2009 Jul 16. PMID:19609254 doi:10.1038/ni.1779

[3] Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009 Aug 7;138(3):576-91. doi: 10.1016/j.cell.2009.06.015. Epub 2009 Jul, 23. PMID:19631370 doi:10.1016/j.cell.2009.06.015

[4] Canella D, Praz V, Reina JH, Cousin P, Hernandez N. Defining the RNA polymerase III transcriptome: Genome-wide localization of the RNA polymerase III transcription machinery in human cells. Genome Res. 2010 Jun;20(6):710-21. PMID:20413673 doi:10.1101/gr.101337.109

[5] Girbig M, Misiaszek AD, Vorländer MK, Lafita A, Grötsch H, Baudin F, Bateman A, Müller CW. Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states. Nat Struct Mol Biol. 2021 Feb;28(2):210-219. PMID:33558764 doi:10.1038/s41594-020-00555-5

[6] Hou H, Li Y, Wang M, Liu A, Yu Z, Chen K, Zhao D, Xu Y. Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine. Nat Commun. 2021 Oct 21;12(1):6135. PMID:34675218 doi:10.1038/s41467-021-26402-9

[7] Van Bortle K, Marciano DP, Liu Q, Chou T, Lipchik AM, Gollapudi S, Geller BS, Monte E, Kamakaka RT, Snyder MP. A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA. Nat Commun. 2022 May 30;13(1):3007. PMID:35637192 doi:10.1038/s41467-022-30323-6

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

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9fss

RNA Polymerase III Class III Open Mini Pre-Initiation complex 2 (OC2-mini)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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