POLR2A, DNA-directed RNA polymerase II subunit RPB1
Enzyme Classification 184.108.40.206
Also Known as
RPB1_HUMAN, POLR2A, POLR2
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (PubMed:24207025). Methylation and dimethylation have a repressive effect on target genes expression., (Microbial infection) Acts as an RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome. Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with ATF7IP. Interacts with DDX5. Interacts with WWP2. Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2, MYO1C, PAF1 and SFRS19. Interacts (via C-terminus) with CMTR1, CTDSP1 and SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2 (PubMed:15563843). Interacts with FUS.