User:Jordan Scott/Sandbox RNA polII: Difference between revisions

Rpb1 also has a CTD that contains heptad repeats of YSPTSPS.<ref name="CTD">PMID: 17685222</ref>(G) This region serves as the main control point for RNAP II. The CTD experiences various conformation changes based on it being in a hypo or hyper phosphorylation state. The heptad repeats may also exist in several forms with one repeat having 16 known states.<ref name="CTD"/> These states form a CTD code that is used to regulate the various stages of transcription and mRNA processing. The CTD is also shown to a part of cell cycle regulation as CDK/cyclins involved in the cell cycle modify the CTD and coordinate gene expression.<ref name="CTD"/> (G) While RNAP II is capable of transcription by itself it is non-selective of any particular DNA region. However some mutageneis studies have shown that RNAP II may have some role in selectivity.<ref name="rich"/> To properly recognize regions upstream of the gene's transcription start site it requires several general transcription factors that are selective for these regions known as promoters and positions RNAP to accurately begin transcription.<ref name="meyers"/> (B) These GTF's and other accessory proteins called SRBs are necessary for accurate transcription and together with the RNAP II core enzyme form the RNAP holoenzyme.

In both eukaryotes and prokaryotes, the basic mechanism for initiating transcription is the same: protein factors selectively bind to promoter regions on DNA. Prokaryotes use sigma factors while eukaryotes use a complex of 6 general initiation factors(GIFs). The combination of all the transcription factors bound to the DNA promoter region, in complex with RNAP II, is known as the preinitiation complex. This complex is necessary for an accurate initiation. The formation of the PIC occurs in an ordered pathway, beginning with the TATA box which is a promoter region on DNA at position -27.

1. <scene name='86/862225/Tfiid/5'>TFIID</scene> is highly conserved among eukaryotes. It recognizes and binds the TATA region of DNA. This is facilitated by a subunit named the TATA-binding protein (TBP). This subunit binding also causes major deformations in the helix which may be important for further binding of the PIC units.  

2. <scene name='86/862225/Tfiib/1'>TFIIB</scene> is the second to join the PIC. It is thought to be responsible for stabilizing the TBP/DNA complex and tethering the TFIID-DNA complex to RNAP I. It is also important in specifying the the TSS. In vitro studies have shown that accurate initiation can occur with only TFIID, TFIIB, and RNAP II suggesting that tese two subunits serve to position RNAP. . Mutagenesis studies also suggest that it works as a bridge between TFIID and pol II.

3. <scene name='86/862225/Tfiif/1'>TFIIF</scene> binds directly to RNAP II and forms a very stable complex. It then escorts RNAP II to the promoter TFIIF also increases specificity and efficiency of transcription. It also acts similarly to bacterial sigma factor by inhibiting and reversing RNAP II binding to nonpromoter sites. (F)

4.<scene name='86/862225/Tfiie/3'>TFIIE</scene> is required to begin transcription even though RNAP II is bound to DNA before TFIIE binds. Once bound it recruits TFIIH.  

5.<scene name='86/862225/Tfiih/1'>TFIIH</scene> supports catalytic activity such as DNA ATPase, DNA helicase, and a kinase that phosphorylates the CTD of RPB1.(F) Some of its subunits are also components of DNA repair machinery. It is the last TF to bind and completes the <scene name='82/824648/Pic/3'>PIC</scene>.  

6.<scene name='82/824648/Tfiia/3'>TFIIA</scene> is a co-activator that helps regulate PIC assembly. It was initially thought to be essential for activity.  It serves as an enhancer and stabilizes the early complexes. It also neutralizes transcription repressors. The mechanism is unknown but it is thought to either increase TBP affinity for DNA or displace repressors. (f)