Negative elongation factor

The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E. Micro-sequencing analysis demonstrated that NELF-B was the protein previously identified as being encoded by the gene COBRA1. 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. == Function and Interactions ==

NELF is located in the nucleus. NELF binds in a stable complex with DSIF (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB)-sensitivity inducing factor) and RNA polymerase II together, but not with either alone. Due to its role in transcription, NELF is also a key player in the negative function of DSIF. NELF also works with DSIF to inhibit the speed of Pol II during the elongation phase in transcription. However, many mechanisms by which NELF and DSIF operate remain unclear. • NELF-C/D: ARAF1, PCF11, and KAT8. • NELF-E: NELF-B and HIV TAR RNA. • NELF undergoes Phase separation in vitro and Condensation in vivo == Clinical Significance ==

The NELF complex is also possibly a player in the enlistment of gene PCF11 to the stopped Pol II in HIV-1 latency. Pol II pausing controlled by NELF is a key source of R-loop aggregation in mammary epithelial cells that are BRCA1-deficient, which could ultimately lead to tumorigenesis. == References ==