Negative elongation factor

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).^[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]

References