DNA-directed RNA polymerase III subunit RPC1

Function

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. 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. 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. 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.

Classification

Family (Pfam)

PF04997 RNA_pol_Rpb1_1, PF00623 RNA_pol_Rpb1_2, PF04983 RNA_pol_Rpb1_3, PF05000 RNA_pol_Rpb1_4, PF04998 RNA_pol_Rpb1_5

InterPro

RNA_pol_asu, RNA_pol_N, RNA_pol_Rpb1_1, RNA_pol_Rpb1_3, RNA_pol_Rpb1_3_sf, RNA_pol_Rpb1_4, RNA_pol_Rpb1_5, RNA_pol_Rpb1_clamp_domain, RNAP_III_Rpc1_C, RNAP_III_RPC1_N, Rpb1_funnel_sf, RPC1

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 29

• 7A6H EM 3.30A
• 7AE1 EM 2.80A
• 7AE3 EM 3.10A
• 7AEA EM 3.40A
• 7AST EM 4.00A
• 7D58 EM 2.90A
• 7D59 EM 3.10A
• 7DN3 EM 3.50A
• 7DU2 EM 3.35A
• 7FJI EM 3.60A
• 7FJJ EM 3.60A
• 8ITY EM 3.90A
• … and 17 more

A predicted model is available from AlphaFold.

Gene Ontology · 20

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005666 RNA polymerase III complex
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0003899 DNA-directed RNA polymerase activity
• GO:0071667 DNA/RNA hybrid binding
• GO:0000287 magnesium ion binding
• GO:0008270 zinc ion binding
• GO:0051607 defense response to virus
• GO:0006351 DNA-templated transcription
• GO:0045087 innate immune response
• GO:0032728 positive regulation of interferon-beta production
• GO:0006386 termination of RNA polymerase III transcription
• GO:0006383 transcription by RNA polymerase III
• GO:0006384 transcription initiation at RNA polymerase III promoter
• GO:0042797 tRNA transcription by RNA polymerase III

Disease associations

• Wiedemann-Rautenstrauch syndrome MONDO:0009910
• leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism MONDO:0011897

Drugs targeting this protein · 1

• TAS-106 inhibitor

Related proteins · sequence + function similarity

• DNA-directed RNA polymerase III subunit RPC1 1.00
• DNA-directed RNA polymerase III subunit RPC1 1.00
• DNA-directed RNA polymerase III subunit 1 0.95
• DNA-directed RNA polymerase III subunit RPC1 0.94
• DNA-directed RNA polymerase III subunit RPC1 0.93
• DNA-directed RNA polymerase III subunit rpc1 0.92
• DNA-directed RNA polymerase I subunit A 0.91
• DNA-directed RNA polymerase III subunit rpc1 0.91
• DNA-directed RNA polymerase I subunit rpa1 0.91
• Probable DNA-directed RNA polymerase II subunit RPB1 homolog 0.90
• DNA-directed RNA polymerase II subunit RPB1 0.89
• DNA-directed RNA polymerase II subunit RPB1 0.89

Co-cited proteins · studied together in the literature

• DNA-directed RNA polymerase III subunit RPC2 12 shared papers
• DNA-directed RNA polymerase III subunit RPC3 12 shared papers
• DNA-directed RNA polymerase III subunit RPC6 10 shared papers
• DNA-directed RNA polymerase III subunit RPC4 10 shared papers
• DNA-directed RNA polymerase III subunit RPC5 10 shared papers
• DNA-directed RNA polymerase III subunit RPC8 9 shared papers
• DNA-directed RNA polymerase III subunit RPC10 9 shared papers
• DNA-directed RNA polymerase III subunit RPC7 10 shared papers
• DNA-directed RNA polymerase III subunit RPC9 9 shared papers
• DNA-directed RNA polymerases I and III subunit RPAC2 8 shared papers
• DNA-directed RNA polymerases I and III subunit RPAC1 7 shared papers
• DNA-directed RNA polymerases I, II, and III subunit RPABC2 6 shared papers

Literature · 25 cited papers

• A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A non-coding RNA. Nat. Commun. · 2022
• Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine. Nat. Commun. · 2021
• Structure of human RNA polymerase III elongation complex. Cell Res. · 2021
• Structural insights into transcriptional regulation of human RNA polymerase III. Nat. Struct. Mol. Biol. · 2021
• Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states. Nat. Struct. Mol. Biol. · 2021
• Structure of human RNA polymerase III. Nat. Commun. · 2020
• Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations. Hum. Genet. · 2018
• Bi-allelic POLR3A loss-of-function variants cause autosomal-recessive Wiedemann-Rautenstrauch syndrome. Am. J. Hum. Genet. · 2018
• Specific combinations of biallelic POLR3A variants cause Wiedemann-Rautenstrauch syndrome. J. Med. Genet. · 2018
• Neonatal progeriod syndrome associated with biallelic truncating variants in POLR3A. Am. J. Med. Genet. A · 2016
• Novel compound heterozygous mutations of POLR3A revealed by whole-exome sequencing in a patient with hypomyelination. Brain Dev. · 2014
• Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. J. Med. Genet. · 2013
• … and 13 more in the literature graph