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

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RNAP II is responsible for the synthesis of pre-mRNA and snRNs. It is 550 kDa and made of 12 subunits that range from 220-10 kDa. The subunits are highly conserved to the point that mammalian subunits can substitute with yeast subunits are there are little to no defects.(B0) There are two large sub units t and 10 smaller subunits, some of which are shared with RNAPs I and III.  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. (A) 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. (B) These GTF's and other accessory proteins called SRBs are necessary for accurate transcription and together with thw RNAP II core enzyme form the RNAP holoenzyme.
RNAP II is responsible for the synthesis of pre-mRNA and snRNs. It is 550 kDa and made of 12 subunits that range from 220-10 kDa. The subunits are highly conserved to the point that mammalian subunits can substitute with yeast subunits are there are little to no defects.(B0) There are two large sub units t and 10 smaller subunits, some of which are shared with RNAPs I and III.  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. (A) 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. (B) These GTF's and other accessory proteins called SRBs are necessary for accurate transcription and together with thw RNAP II core enzyme form the RNAP holoenzyme.


'''RNA polymerase II''' (RNAP II) is an enzyme that transcribes protein-encoding genes, and it therefore is responsible for the synthesis of mRNA. There are three RNA polymerase enzymes found in eukaryotic nuclei but RNAP II is the most studied. RNAP II is a 550 kDa multi-protein complex that includes 12 subunits. Several transcription factors are used to bind promoters upstream of the start site and are necessary for joining RNAP II and DNA. Bound RNAP II transcribes DNA into a strand of messenger RNA (mRNA). mRNA is a single stranded RNA molecule that is complementary to the template strand of DNA and matches the coding strand. In prokaryotes the transcript is ready for translation, but in eukaryotes post transcriptional modifications are required.  The mRNA stand transports genetic information from DNA to the ribosome,where the code will be translated into an amino acid acid sequence to form proteins.
 


===Subunits===
===Subunits===
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Source: https://www.pnas.org/content/94/1/151.
Source: https://www.pnas.org/content/94/1/151.
1. <scene name='82/824648/Tfiid-tbp/3'>TFIID</scene> is highly conserved among eukaryotes. It recognizes and binds the TATA box. This is facilitated by a subunit named the TATA-binding protein (TBP). This subunit also causes slight deformations in the helix which may be important for further binding of the PIC units.
1. <scene name='82/824648/Tfiid-tbp/3'>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='82/824648/Tfiib/3'>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-RNAPII complex to DNA. It is also important in specifying the the TSS and insuring proper directionality . If the orientation is wrong unfavorable interactions form. Mutagenesis studies also suggest that it works as a bridge between TFIID and pol II.


3. <scene name='82/824648/Tfiif/5'>TFIIF</scene> binds directly to RNAP II and escorts it to the promoter while TFIIB helps the complex bind correctly.  
2. <scene name='82/824648/Tfiib/3'>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.


4. <scene name='82/824648/Tfiie/4'>TFIIE</scene> and are sequentially recruited which completes the <scene name='82/824648/Pic/3'>PIC</scene>.
3. <scene name='82/824648/Tfiif/5'>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 similairy to bacterial sigma factor by inhibiting and reversing RNAP II binding to nonpromoter sites. (F)


5.<scene name='82/824648/Tfiih/3'>TFIIH</scene>
4. <scene name='82/824648/Tfiie/4'>TFIIE</scene> is required to begin transcription even though RNAP II is bound to DNA before TFIIE binds. Once bound it recruits the last TF,  TFIIH.


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 allows for inhibitory effect to be reduced and activators to be more effective.
5.<scene name='82/824648/Tfiih/3'>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)


Once the <scene name='82/824648/Pic/3'>PIC</scene> is formed, <scene name='82/824648/Rnap_ii/1'>RNAP II</scene> initiates RNA synthesis and produces a short transcript. When RNAP II becomes phosphorylated, it releases some of the GTFs from the complex and moves away from the promoter. TFIID stays bound to the promoter and can reinitiate transcription and help with successive transcription. The transcription factors are replaced by a new six-protein complex call the Elongator. TFIIF and TFIIH both remain associated with RNAP II during elongation.   
Once the <scene name='82/824648/Pic/3'>PIC</scene> is formed, <scene name='82/824648/Rnap_ii/1'>RNAP II</scene> initiates RNA synthesis and produces a short transcript. When RNAP II becomes phosphorylated, it releases some of the GTFs from the complex and moves away from the promoter. TFIID stays bound to the promoter and can reinitiate transcription and help with successive transcription. The transcription factors are replaced by a new six-protein complex call the Elongator. TFIIF and TFIIH both remain associated with RNAP II during elongation.   
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