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Structure of paused transcription complex Pol II-DSIF-NELF - post-translocated
Structural highlights
FunctionNELFE_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 PubMedMetazoan 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. References
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