In molecular biology, NELF (negative elongation factor) is a four-subunit protein (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).
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. 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.
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. NELF homologues exist in some metazoans (e.g. insects and vertebrates) but have not been found in plants, yeast, or nematode (worms).