| Structural highlights
Disease
NELFA_HUMAN Wolf-Hirschhorn syndrome.
Function
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.[1] [2] [3]
Publication Abstract from PubMed
Transcription regulation in metazoans often involves promoter-proximal pausing of RNA polymerase (Pol) II, which requires the 4-subunit negative elongation factor (NELF). Here we discern the functional architecture of human NELF through X-ray crystallography, protein crosslinking, biochemical assays, and RNA crosslinking in cells. We identify a NELF core subcomplex formed by conserved regions in subunits NELF-A and NELF-C, and resolve its crystal structure. The NELF-AC subcomplex binds single-stranded nucleic acids in vitro, and NELF-C associates with RNA in vivo. A positively charged face of NELF-AC is involved in RNA binding, whereas the opposite face of the NELF-AC subcomplex binds NELF-B. NELF-B is predicted to form a HEAT repeat fold, also binds RNA in vivo, and anchors the subunit NELF-E, which is confirmed to bind RNA in vivo. These results reveal the three-dimensional architecture and three RNA-binding faces of NELF.
Architecture and RNA binding of the human negative elongation factor.,Vos SM, Pollmann D, Caizzi L, Hofmann KB, Rombaut P, Zimniak T, Herzog F, Cramer P Elife. 2016 Jun 10;5. pii: e14981. doi: 10.7554/eLife.14981. PMID:27282391[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Zollino M, Lecce R, Fischetto R, Murdolo M, Faravelli F, Selicorni A, Butte C, Memo L, Capovilla G, Neri G. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. Am J Hum Genet. 2003 Mar;72(3):590-7. Epub 2003 Jan 30. PMID:12563561 doi:http://dx.doi.org/S0002-9297(07)60575-8
- ↑ 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
- ↑ Vos SM, Pollmann D, Caizzi L, Hofmann KB, Rombaut P, Zimniak T, Herzog F, Cramer P. Architecture and RNA binding of the human negative elongation factor. Elife. 2016 Jun 10;5. pii: e14981. doi: 10.7554/eLife.14981. PMID:27282391 doi:http://dx.doi.org/10.7554/eLife.14981
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