Negative elongation factor

In molecular biology, NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20-60 nucleotides downstream from the transcription start site (TSS).[1]

Structure

The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2). Microsequencing analysis demonstrated that NELF-B was the protein previously identified as the protein encoded by the gene COBRA1, and was shown to interact with BRCA1.[2] It is unknown whether or not NELF-C and NELF-D are peptides resulting from the same mRNA with different translation initiation sites, possibly differing only in an extra 9 amino acids for NELF-C at the N-terminus, or peptides from different mRNAs entirely. A single NELF complex consists of either NELF-C or NELF-D but not both. NELF-E is also known as RDBP.[2][3]

NELF binds in a stable complex with DSIF and RNA polymerase II together, but not with either alone. P-TEFb (positive transcription elongation factor b) inhibits the effect of NELF and DSIF on Pol II elongation, via its phosphorylation of serine-2 of the C-terminal domain of Pol II, and the SPT5 subunit of DSIF, causing dissociation of NELF.[2] NELF homologues exist in some metazoans (e.g. insects and vertebrates) but have not been found in plants, yeast, or nematode (worms).[2]

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References
  1. Adelman, Karen; Lis, John T. (18 September 2012). "Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans". Nature Reviews Genetics. 13 (10): 720–731. doi:10.1038/nrg3293. PMC 3552498. PMID 22986266.
  2. Narita, Takashi; Yamaguchi, Yuki; Yano, Keiichi; Sugimoto, Seiji; Chanarat, Sittinan; Wada, Tadashi; Kim, Dong-ki; Hasegawa, Jun; Omori, Masashi; Inukai, Naoto; Endoh, Masaki; Yamada, Tomoko; Handa, Hiroshi (15 March 2003). "Human Transcription Elongation Factor NELF: Identification of Novel Subunits and Reconstitution of the Functionally Active Complex". Molecular and Cellular Biology. 23 (6): 1863–1873. doi:10.1128/MCB.23.6.1863-1873.2003. PMC 149481. PMID 12612062.
  3. Yamaguchi, Yuki; Takagi, Toshiyuki; Wada, Tadashi; Yano, Keiichi; Furuya, Akiko; Sugimoto, Seiji; Hasegawa, Jun; Handa, Hiroshi (April 1999). "NELF, a Multisubunit Complex Containing RD, Cooperates with DSIF to Repress RNA Polymerase II Elongation". Cell. 97 (1): 41–51. doi:10.1016/S0092-8674(00)80713-8. PMID 10199401.


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