Negative elongation factor
NELF (Negative elongation factor) is a four subunit protein (NELF-A, NELF-B, NELF-C or NELF-D, NELF-E) that affects transcription by RNA polymerase II. Subunit NELF-E is also known as RDBP. The NELF-A subunit is encoded by the gene WHSC2, Wolf-Hirschhorn syndrome candidate 2. NELF-C and NELF-D are probably peptides resulting from the same mRNA with different translation initiation site, possibly differing only in an extra 9 amino acids for NELF-C at the N-terminus. Or, it is possible they arise from different mRNAs. A single NELF complex consists of either NELF-C or NELF-D but not both. Microsequencing analysis showed that NELF-B was the protein previously identified as the protein encoded by the gene COBRA1, and shown to interact with BRCA1.
NELF binds in a stable complex with DSIF and RNA Polymerase II together, but not with either alone. P-TEFb inhibits the effect of NELF and DSIF on Pol II elongation, via its phosphorylation of Serine 2 on the C-terminal domain of Pol II, and the SPT5 subunit of DSIF, causing dissociation of NELF. NELF homologues exist in some metazoans (e.g. insects and vertebrates) but have not been found in plants, yeast, or nematode (worms).
- Yamaguchi, Y.; Takagi, T.; Wada, T.; Yano, K.; Furuya, A.; Sugimoto, S.; Hasegawa, J.; Handa, H. (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.
- 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 (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.
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