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.^[1][2] 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.^[2]

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.^[2] NELF homologues exist in some metazoans (e.g. insects and vertebrates) but have not been found in plants, yeast, or nematode (worms).^[2]

References

1. ^ 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. 
2. ^ ^{a b c d} 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149481. 

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