What is NELF and DSIF?
Metazoan gene regulation often involves the pausing of RNA polymerase II (Pol II) in the promoter-proximal region. Here we report the cryo-electron microscopy structure of a paused transcription elongation complex containing Sus scrofa Pol II and Homo sapiens DSIF and NELF at 3.2 Å resolution.
What is the function of the elongation factor Tfiis?
TFIIS is perhaps the best characterized elongation factor (7). In vitro, TFIIS stimulates arrested Pol II to cleave the nascent transcript that has fallen out of register with template DNA (7, 8). This generates a new 3′ end in the nascent mRNA that is used by Pol II to resume transcription.
What is NELF?
The negative elongation factor (NELF) also has no effect on RNA polymerase II alone, but the combination of NELF and DSIF is able to slow the elongation rate and cause the polymerase to reside longer at pause sites. In this way, NELF and DSIF act in exactly the opposite way as TFIIF, which reduces pause time.
What is the function of NELF?
It is presumed that an important function of NELF is to participate in stabilizing the Pol II-DSIF complex, resulting in a significant impact on transcription of its target genes.
What phosphorylates NELF?
Finally, P-TEFb phosphorylates NELFe (RD). This phosphorylation releases NELF from the double-stranded RNA and leads to some read through transcription (Fujinaga et al., 2004).
Is NELF phosphorylated?
P-TEFb-mediated phosphorylation of NELF-A is essential for pause release. P-TEFb has been shown to phosphorylate NELF-E (21), but whether NELF-A could be phosphorylated by P-TEFb is not clear.
How does elongation occur in transcription?
Elongation is the addition of nucleotides to the mRNA strand. During this process, an adenine (A) in the DNA binds to an uracil (U) in the RNA. Termination is the ending of transcription, and occurs when RNA polymerase crosses a stop (termination) sequence in the gene.
Is the NELF A positive or negative elongation factor?
In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (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).
How does P-TEFb inhibit NELF and DSIF?
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. However, many mechanisms by which NELF and DSIF operate remain unclear.
What is the gene for negative elongation factor?
The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2). Micro-sequencing analysis demonstrated that NELF-B was the protein previously identified as being encoded by the gene COBRA1.
What are the four subunits of the NELF gene?
The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E. The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2).