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The nuclear capping enzyme complex (CEC) required for 5’-end capping may be found bound to the RNA polymerase II (Pol II) before transcription starts. As soon as the 5' end of the new transcript emerges the enzymes transfer to it and begin the capping process (this mechanism to ensure capping is similar to that used for polyadenylation).

The capping enzyme complex is also known as the cap-synthesizing and cap-binding complex (CBC).[1] The role of the capping enzymes and cap methyltransferases in transcription elongation may be gene-specific.[1]

Contents

Capping

RNA polymerase II nascent transcripts are capped during a pause before elongation.[2] Consistent with capping enzyme binding, TFIIH-phosphorylated CTD stimulates guanylylation.[2]

The 7-methylguanosine cap is formed by the action of three enzymes:

  1. RNA 5’-triphosphatase (RTP),
  2. RNA guanylyltransferase (RGT), and
  3. RNA (guanine-7-) methyltransferase (RNMT).[1]

Capping enzymes

5'-caps are added to nascent Pol II transcripts (pre-mRNA) when they reach a chain length of 25–30 nucleotides.[3] This is accomplished by the direct binding of the capping enzyme (RNGTT in humans) to the phosphorylated form of RNA polymerase II carboxy-terminal domain (CTD).[4]

Eukaryotic capping enzymes are bifunctional with both RNA 5’-triphosphatase (RTP) and RNA guanylyltransferase (RGT) activities. In concert with RNA (guanine-7-) methyltransferase (EC 2.1.1.56, abbreviated RNMT in humans), they selectively modify the 5’ ends of newly initiated RNA polymerase II (Pol II) transcripts by adding a 7-methylguanosine cap soon after transcription initiation.[2][1]

The capping enzyme apparently does not associate with basal transcription initiation factors.[4]

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RNGTT

RNA guanylyltransferase and 5’-phosphatase is symbolized with RNGTT. The eukaryotic capping enzyme is bifunctional with both RNA 5’-triphosphatase (RTP) and RNA guanylyltransferase (RGT) activities. The reactions catalyzed are

  1. GTP + (5')pp-Pur-mRNA <=> diphosphate + G(5')ppp-Pur-mRNA : mRNA guanylyltransferase EC 2.7.7.50, where p is phosphate, and
  2. A 5'-phosphopolynucleotide + H2O <=> a polynucleotide + phosphate : Polynucleotide 5'-phosphatase EC 3.1.3.33.

In humans this enzyme is GeneID: 8732.

RNMT

RNA (guanine-7-) methyltransferase catalyzes the following reaction:

S-adenosyl-L-methionine + G(5')pppR-RNA <=> S-adenosyl-L-homocysteine + m(7)G(5')pppR-RNA :[5] mRNA (guanine-N(7)-)-methyltransferase (RNMT) EC 2.1.1.56 GeneID: 8751. “R-” refers to the first transcribed nucleotide of the pre-mRNA. “p” is a phosphate group.

Additional complex member

Cyclin-dependent kinase 7 (CDK7) is a subunit of the basic transcription factor TFIIH.

RNA polymerase II holoenzyme

The enzymes for capping can only bind to RNA polymerase II ensuring specificity to only these transcripts, which are almost entirely mRNA. The finding that the capping enzyme is recruited to the RNA polymerase II holoenzyme via binding to the phosphorylated CTD (P-CTD) explains the selective capping of Pol II transcripts and may couple capping to the switch from transcription initiation to elongation.[2]

Pause

The RNA polymerase II holoenzyme is recruited to euchromatin with the CTD unphosphorylated.[6] During transcription initiation, the CTD is phosphorylated on Serine number 5 (Ser5) by cyclin-dependent kinase 7 (CDK7), which is a subunit of the basic transcription factor TFIIH. Upon phosphorylation, the polymerase pauses. The enzymes which create the 7-methylguanosine cap in eukaryotes is recruited preferentially to the RNA polymerase II CTD when it is phosphorylated on Ser5.[1] Release from pausing into transcription elongation is partially dependent on these enzymes.[1]

After transcription initiates, RNA polymerase II ‘pauses’ and transcription stops. Many eukaryotic elongation factors function by either preventing or overcoming Pol II transcriptional pausing.[2] Release from this arrest into productive transcription elongation is a major point in the control of transcription.[7]

See also

References

  1. ^ a b c d e f Cowling VH (Jan 2010). "Regulation of mRNA cap methylation". Biochem J. 425 (Pt 2): 295–302. doi:10.1042/BJ20091352. PMID 20025612. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825737/?tool=pubmed. 
  2. ^ a b c d e Wen Y, Shatkin AJ (Jul 1999). "RNA polymerase II nascent transcripts are capped during pausing before elongation". Genes Dev. 13 (14): 1774–9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC316881/?tool=pmcentrez. 
  3. ^ Coppola JA, Field AS, Luse DS (1983). [Expression error: Unexpected < operator "Promoter-proximal pausing by RNA polymerase II in vitro: Transcripts shorter that 20 nucleotides are not capped"]. Proc Natl Acad Sci. 80: 1251–5. 
  4. ^ a b Cho EJ, Takagi T, Moore CR, Buratowski S (1997). [Expression error: Unexpected < operator "mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain"]. Genes & Dev. 11: 3319–26. 
  5. ^ "ENZYME entry: EC 2.1.1.56". http://www.expasy.org/cgi-bin/nicezyme.pl?2.1.1.56. 
  6. ^ Chapman RD, Heidemann M, Hintermair C, Eick D (2008). [Expression error: Unexpected < operator "Molecular evolution of the RNA polymerase II CTD"]. Trends Genet. 24: 289–96. 
  7. ^ Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA (2007). [Expression error: Unexpected < operator "A chromatin landmark and transcription initiation at most promoters in human cells"]. Cell. 130: 77–88. 

Further reading

External links


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