| Structural highlights
Disease
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
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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
References
- ↑ 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
- ↑ Ramsay EP, Abascal-Palacios G, Daiß JL, King H, Gouge J, Pilsl M, Beuron F, Morris E, Gunkel P, Engel C, Vannini A. Structure of human RNA polymerase III. Nat Commun. 2020 Dec 17;11(1):6409. PMID:33335104 doi:10.1038/s41467-020-20262-5
- ↑ 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
- ↑ Wang Q, Li S, Wan F, Xu Y, Wu Z, Cao M, Lan P, Lei M, Wu J. Structural insights into transcriptional regulation of human RNA polymerase III. Nat Struct Mol Biol. 2021 Feb;28(2):220-227. PMID:33558766 doi:10.1038/s41594-021-00557-x
- ↑ Li L, Yu Z, Zhao D, Ren Y, Hou H, Xu Y. Structure of human RNA polymerase III elongation complex. Cell Res. 2021 Jul;31(7):791-800. PMID:33674783 doi:10.1038/s41422-021-00472-2
- ↑ 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
- ↑ Sepehri S, Hernandez N. The largest subunit of human RNA polymerase III is closely related to the largest subunit of yeast and trypanosome RNA polymerase III. Genome Res. 1997 Oct;7(10):1006-19. PMID:9331371 doi:10.1101/gr.7.10.1006
|
