What does P TEFb phosphorylation?

What does P TEFb phosphorylation?

The Positive Transcription Elongation Factor b (P-TEFb) phosphorylates Ser2 residues of the C-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II and is essential for the transition from transcription initiation to elongation in vivo.

What is promoter proximal pausing?

Pol II pauses in the proximity of the promoter on a large fraction of transcribed genes. Transcription initiation and elongation of transcripts are under distinct control. Induced gene expression can thus be due to enhanced initiation and/or stimulated elongation.

What is the role of P-TEFb during elongation?

The positive transcription elongation factor b (P-TEFb) is a cyclin-dependent kinase that controls the elongation phase of transcription by RNA polymerase II (RNAPII). In those organisms, the function of P-TEFb is influenced negatively by HEXIM proteins and 7SK snRNA and positively by a variety of recruiting factors.

What is Tfiis?

Transcription elongation factor IIS (TFIIS) is a component of RNA polymerase II preinitiation complexes, and is required for preinitiation complex assembly and stability. . The association of TFIIS with a promoter depends on functional preinitiation complex components including Mediator and the SAGA complex. .

What is transcriptional pausing?

Abstract. Transcriptional pausing underlies regulation of cellular RNA biogenesis. A consensus pause sequence that acts on RNA polymerases (RNAPs) from bacteria to mammals halts RNAP in an elemental paused state from which longer-lived pauses can arise.

What are proximal promoter elements?

Promoter-proximal elements – Any regulatory sequence in eukaryotic DNA that is located close to (within 200 base pairs) a promoter and binds a specific protein thereby modulating transcription of the associated protein coding gene. Many genes are controlled by multiple promoter-proximal elements.

What is elongation in transcription?

Basically, elongation is the stage when the RNA strand gets longer, thanks to the addition of new nucleotides. During elongation, RNA polymerase “walks” along one strand of DNA, known as the template strand, in the 3′ to 5′ direction.

Why is transcriptional pausing important?

Transcriptional pausing underlies regulation of cellular RNA biogenesis. Although the structural foundations of pauses prolonged by backtracking or nascent RNA hairpins are recognized, the fundamental mechanism of the elemental pause is less well-defined.

What is RNA polymerase pausing?

RNA polymerase II (Pol II) pauses downstream of the transcription initiation site before beginning productive elongation. This pause is a key component of metazoan gene expression regulation. We propose that paused Pol II helps prevent new initiation between transcription bursts, which may reduce noise.

How can a mutation in a promoter affect gene expression?

Mutations in the promoter region resulted in a change in DNA binding pattern of the AP-2 transcription factor. Modulation of transcription factors binding pattern might lead to a change of sequence-specific interaction between DNA-protein or protein-protein in the transcription initiation complex.

What are introns and exons?

An intron is a portion of a gene that does not code for amino acids. The parts of the gene sequence that are expressed in the protein are called exons, because they are expressed, while the parts of the gene sequence that are not expressed in the protein are called introns, because they come in between the exons.

Does P-TEFb phosphorylate the CTD?

P-TEFb had been shown to have broad substrate specificity in vitro and will phosphorylate the large subunit of both DSIF and TFIIF. Although the CTD is phosphorylated by P-TEFb and is required for the function of P-TEFb in transcription, there may be other important functional phosphorylation targets.

What is the function of P-TEFb?

P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs.

How is P-TEFb targeted by HIV Tat protein?

Importantly, for the AIDS virus, HIV, P-TEFb is targeted by the HIV Tat protein which bypasses normal cellular P-TEFb control and directly brings P-TEFb to the promoter proximal paused polymerase in the HIV genome.

What are the components of PTEFb complex?

The first complex is “core P-TEFb” and it is composed of CDK9, cyclinT1, and Brd4 (Yang et al., 2005 ). Brd4 contains two bromodomains that bind to acetyllysine residues of histones H3 and H4 found in active chromatin.