Biology:Termination factor
In molecular biology, a termination factor is a protein that mediates the termination of RNA transcription by recognizing a transcription terminator and causing the release of the newly made mRNA. This is part of the process that regulates the transcription of RNA to preserve gene expression integrity and are present in both eukaryotes and prokaryotes, although the process in bacteria is more widely understood.[1] The most extensively studied and detailed transcriptional termination factor is the Rho (ρ) protein of E. coli.[2]
Prokaryotic
Prokaryotes use one type of RNA polymerase, transcribing mRNAs that code for more than one type of protein. Transcription, translation and mRNA degradation all happen simultaneously. Transcription termination is essential to define boundaries in transcriptional units, a function necessary to maintain the integrity of the strands and provide quality control. Termination in E. coli may be Rho dependent, utilizing Rho factor, or Rho independent, also known as intrinsic termination. Although most operons in DNA are Rho independent, Rho dependent termination is also essential to maintain correct transcription.[1]
ρ factor The Rho protein is an RNA translocase that recognizes a cytosine-rich region of the elongating mRNA, but the exact features of the recognized sequences and how the cleaving takes place remain unknown. Rho forms a ring-shaped hexamer and advances along the mRNA, hydrolyzing ATP toward RNA polymerase (5' to 3' with respect to the mRNA).[3][4] When the Rho protein reaches the RNA polymerase complex, transcription is terminated by dissociation of the RNA polymerase from the DNA. The structure and activity of the Rho protein is similar to that of the F1 subunit of ATP synthase, supporting the theory that the two share an evolutionary link.[4]
Rho factor is widely present in different bacterial sequences and is responsible for the genetic polarity in E. coli. It works as a sensor of translational status, inhibiting non-productive transcriptions,[5] suppressing antisense transcriptions and resolving conflicts that happen between transcription and replication.[6] The process of termination by Rho factor is regulated by attenuation and antitermination mechanisms, competing with elongation factors for overlapping utilization sites (ruts and nuts), and depends on how fast Rho can move during the transcription to catch up with the RNA polymerase and activate the termination process.[7]
Inhibition of Rho dependent termination by bicyclomycin is used to treat bacterial infections. The use of this mechanism along with other classes of antibiotics is being studied as a way to address antibiotic resistance, by suppressing the protective factors in RNA transcription while working in synergy with other inhibitors of gene expression such as tetracycline or rifampicin.[8]
Eukaryotic
The process of transcriptional termination is less understood in eukaryotes, which have extensive post-transcriptional RNA processing, and each of the three types of eukaryotic RNA polymerase have a different termination system.
In RNA polymerase I, Transcription termination factor, RNA polymerase I binds downstream of the pre-rRNA coding regions, causing the dissociation of the RNA polymerase from the template and the release of the new RNA strand.
In RNA polymerase II, the termination occurs via a polyadenylation/cleaving complex. The 3' tail on the ending of the strand is bound at the polyadenylation site, but the strand will continue to code. The newly synthesised ribonucleotides are removed one at a time by the cleavage factors CSTF and CPSF, in a process that is still not fully understood. The remainder of the strand is disengaged by a 5′-exonuclease when the transcription is finished.
RNA polymerase III terminates after a series of uracil polymerization residues in the transcribed mRNA.[1] Unlike in bacteria and in polymerase I, the termination RNA hairpin needs to be upstream to allow for correct cleaving.[9]
See also
References
- ↑ 1.0 1.1 1.2 Molecular Cell Biology 4th edition. New York: W. H. Freeman. 2000.
- ↑ "Terminator still moving forward: expanding roles for Rho factor". Current Opinion in Microbiology 16 (2): 118–24. April 2013. doi:10.1016/j.mib.2012.12.003. PMID 23347833.
- ↑ "Loading Rho to terminate transcription". Cell 114 (2): 157–9. July 2003. doi:10.1016/s0092-8674(03)00554-3. PMID 12887917.
- ↑ 4.0 4.1 "Transcription termination factor rho is an RNA-DNA helicase". Cell 48 (6): 945–52. March 1987. doi:10.1016/0092-8674(87)90703-3. PMID 3030561.
- ↑ "Mechanisms of Bacterial Transcription Termination". Journal of Molecular Biology 431 (20): 4030–4039. April 2019. doi:10.1016/j.jmb.2019.04.003. PMID 30978344.
- ↑ "Learning from the Leaders: Gene Regulation by the Transcription Termination Factor Rho". Trends in Biochemical Sciences 41 (8): 690–699. August 2016. doi:10.1016/j.tibs.2016.05.012. PMID 27325240.
- ↑ "Transcription Elongation Factor NusA Is a General Antagonist of Rho-dependent Termination in Escherichia coli". The Journal of Biological Chemistry 291 (15): 8090–108. April 2016. doi:10.1074/jbc.M115.701268. PMID 26872975.
- ↑ "Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics". The Journal of Antimicrobial Chemotherapy 69 (12): 3227–35. December 2014. doi:10.1093/jac/dku285. PMID 25085655.
- ↑ "Mechanism of eukaryotic RNA polymerase III transcription termination". Science 340 (6140): 1577–80. June 2013. doi:10.1126/science.1237934. PMID 23812715. Bibcode: 2013Sci...340.1577N.
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