This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6gml
From Proteopedia
Structure of paused transcription complex Pol II-DSIF-NELF
Structural highlights
Disease[NELFA_HUMAN] Wolf-Hirschhorn syndrome. Function[RPB9_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. 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. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity). [I3LGP4_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] [SPT4H_HUMAN] component of the drb sensitivity-inducing factor complex (dsif complex), which regulates mrna processing and transcription elongation by rna polymerase ii dsif positively regulates mrna capping by stimulating the mrna guanylyltransferase activity of rngtt/cap1a dsif also acts cooperatively with the negative elongation factor complex (nelf complex) to enhance transcriptional pausing at sites proximal to the promoter transcriptional pausing may facilitate the assembly of an elongation competent rna polymerase ii complex dsif and nelf promote pausing by inhibition of the transcription elongation factor tfiis/s-ii tfiis/s-ii binds to rna polymerase ii at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme cleavage of blocked transcripts by rna polymerase ii promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites dsif can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the hiv- 1 nuclear transcriptional activator, tat dsif acts to suppress transcriptional pausing in transcripts derived from the hiv-1 ltr and blocks premature release of hiv-1 transcripts at terminator sequences [NELFD_HUMAN] Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex.[1] [2] [I3LCB2_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.[PIRNR:PIRNR000779] [NELFA_HUMAN] Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex. Probably required to interact with the RNA polymerase II complex.[3] [4] [5] [SPT5H_HUMAN] Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences.[6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] Publication Abstract from PubMedMetazoan gene regulation often involves the pausing of RNA polymerase II (Pol II) in the promoter-proximal region. Paused Pol II is stabilized by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we report the cryo-electron microscopy structure of a paused transcription elongation complex containing Sus scrofa Pol II and Homo sapiens DSIF and NELF at 3.2 A resolution. The structure reveals a tilted DNA-RNA hybrid that impairs binding of the nucleoside triphosphate substrate. NELF binds the polymerase funnel, bridges two mobile polymerase modules, and contacts the trigger loop, thereby restraining Pol II mobility that is required for pause release. NELF prevents binding of the anti-pausing transcription elongation factor IIS (TFIIS). Additionally, NELF possesses two flexible 'tentacles' that can contact DSIF and exiting RNA. These results define the paused state of Pol II and provide the molecular basis for understanding the function of NELF during promoter-proximal gene regulation. Structure of paused transcription complex Pol II-DSIF-NELF.,Vos SM, Farnung L, Urlaub H, Cramer P Nature. 2018 Aug;560(7720):601-606. doi: 10.1038/s41586-018-0442-2. Epub 2018 Aug, 22. PMID:30135580[25] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||||
Categories: DNA-directed RNA polymerase | Human | Large Structures | Sus scrofa | Cramer, P | Farnung, L | Urlaub, H | Vos, S M | Dsif | Nelf | Pausing | Rna polymerase ii | Transcription
