4jxt

Structural highlights

Function

[RPR1A_HUMAN] Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle.^{[1] [2]} [RPB1_HUMAN] 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. Acts as a 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.^{[3] [4]}

References

1. ↑ Liu J, Liu H, Zhang X, Gao P, Wang J, Hu Z. Identification and characterization of P15RS, a novel P15(INK4b) related gene on G1/S progression. Biochem Biophys Res Commun. 2002 Dec 20;299(5):880-5. PMID:12470661
2. ↑ Ni Z, Olsen JB, Guo X, Zhong G, Ruan ED, Marcon E, Young P, Guo H, Li J, Moffat J, Emili A, Greenblatt JF. Control of the RNA polymerase II phosphorylation state in promoter regions by CTD interaction domain-containing proteins RPRD1A and RPRD1B. Transcription. 2011 Sep-Oct;2(5):237-42. doi: 10.4161/trns.2.5.17803. PMID:22231121 doi:http://dx.doi.org/10.4161/trns.2.5.17803
3. ↑ Kershnar E, Wu SY, Chiang CM. Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes. J Biol Chem. 1998 Dec 18;273(51):34444-53. PMID:9852112
4. ↑ Chang J, Nie X, Chang HE, Han Z, Taylor J. Transcription of hepatitis delta virus RNA by RNA polymerase II. J Virol. 2008 Feb;82(3):1118-27. Epub 2007 Nov 21. PMID:18032511 doi:http://dx.doi.org/10.1128/JVI.01758-07
5. ↑ Ni Z, Xu C, Guo X, Hunter GO, Kuznetsova OV, Tempel W, Marcon E, Zhong G, Guo H, Kuo WH, Li J, Young P, Olsen JB, Wan C, Loppnau P, El Bakkouri M, Senisterra GA, He H, Huang H, Sidhu SS, Emili A, Murphy S, Mosley AL, Arrowsmith CH, Min J, Greenblatt JF. RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation. Nat Struct Mol Biol. 2014 Jul 6. doi: 10.1038/nsmb.2853. PMID:24997600 doi:http://dx.doi.org/10.1038/nsmb.2853