8ui0

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Structure of poised transcription complex Pol II-DSIF-NELF - pre-translocated

Structural highlights

8ui0 is a 10 chain structure with sequence from Homo sapiens, Sus scrofa and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.7Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NELFE_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] [3]

Publication Abstract from PubMed

Metazoan gene expression regulation involves pausing of RNA polymerase (Pol II) in the promoter-proximal region of genes and is stabilized by DSIF and NELF. Upon depletion of elongation factors, NELF appears to accompany elongating Pol II past pause sites; however, prior work indicates that NELF prevents Pol II elongation. Here, we report cryoelectron microscopy structures of Pol II-DSIF-NELF complexes with NELF in two distinct conformations corresponding to paused and poised states. The paused NELF state supports Pol II stalling, whereas the poised NELF state enables transcription elongation as it does not support a tilted RNA-DNA hybrid. Further, the poised NELF state can accommodate TFIIS binding to Pol II, allowing for Pol II reactivation at paused or backtracking sites. Finally, we observe that the NELF-A tentacle interacts with the RPB2 protrusion and is necessary for pausing. Our results define how NELF can support pausing, reactivation, and elongation by Pol II.

Distinct negative elongation factor conformations regulate RNA polymerase II promoter-proximal pausing.,Su BG, Vos SM Mol Cell. 2024 Apr 4;84(7):1243-1256.e5. doi: 10.1016/j.molcel.2024.01.023. Epub , 2024 Feb 23. PMID:38401543[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. ↑ Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell. 1999 Apr 2;97(1):41-51. PMID:10199401
  2. ↑ Yamaguchi Y, Inukai N, Narita T, Wada T, Handa H. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA. Mol Cell Biol. 2002 May;22(9):2918-27. PMID:11940650
  3. ↑ Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H. Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol. 2003 Mar;23(6):1863-73. PMID:12612062
  4. ↑ Su BG, Vos SM. Distinct negative elongation factor conformations regulate RNA polymerase II promoter-proximal pausing. Mol Cell. 2024 Apr 4;84(7):1243-1256.e5. PMID:38401543 doi:10.1016/j.molcel.2024.01.023

Contents


PDB ID 8ui0

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OCA

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