User:Kaitlynwu18/Termination signal
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A termination signal is a sequence that signals the end of transcription or translation.[1] Termination signals bring a stop to transcription, ensuring that only gene-encoding parts of the chromosome are transcribed.[1] Transcription begins at the promoter when RNA polymerase, an enzyme that facilitates transcription of DNA into mRNA, binds to a promoter, unwinds the helical structure of the DNA, and uses the single-stranded DNA as a template to synthesize RNA.[1] Once RNA polymerase reaches the termination signal, transcription is terminated.[1] In bacteria, there are two main types of termination signals: intrinsic and factor-dependent terminators.[2] In the context of translation, a termination signal is the stop codon on the mRNA that elicits the release of the growing peptide from the ribosome.[3]
Termination signals play an important role in regulating gene expression since they mark the end of a gene transcript and determine which DNA sequences are expressed in the cell.[2] Expression levels of certain genes can be increased by inhibiting signal terminators, known as antitermination, which allows for transcription to continue beyond the termination signal site.[2] This can be desirable under specific cell conditions.[2]
Additionally, sometimes, termination signals are overlooked in transcription and translation, resulting in unwanted transcription or translation past the termination signal.[4] To address this issue, termination signals can be optimized to increase termination efficiency.[4]
Bacterial Termination Signals
[edit]The two types of termination signals in bacteria are intrinsic and factor-dependent terminators.[2] Intrinsic termination occurs when a specific sequence on the growing RNA strand elicits detachment of RNA polymerase from the RNA-DNA complex.[2] In E. coli, one intrinsic termination signal consists of an RNA hairpin that has high amounts of guanine and cytosine, as well as a region high in uracil nucleobases.[2]
Factor-dependent terminators require proteins for proper termination.[2] One example is rho-dependent termination, a common termination mechanism found in bacteria that involves the binding of Rho protein to remove RNA polymerase from the DNA-RNA complex.[2]
Antitermination
[edit]Antitermination involves the inhibition of signal terminators.[2] RNA polymerase is prevented from detaching from the RNA in response to a termination signal, increasing downstream gene expression.[2]
Antitermination can occur in a variety of ways.[2] Some antiterminators disrupt termination signals by inhibiting RNA hairpin generation, while other antiterminators are proteins that bind to RNA polymerase and cause RNA polymerase to continue transcription past termination signals.[2] Depending on the environment of the cell, antitermination may be crucial to cell survival.[2] These antitermination mechanisms are crucial when the cell is under stress, allowing for increased expression of downstream genes that are needed under dire circumstances.[2]
Termination Signal Efficiency
[edit]Transcription
[edit]Termination efficiency of T7 RNA polymerase is around 74%, which creates issues when T7 RNA polymerase is used to produce recombinant proteins.[4] In this process, the target gene is inserted into a plasmid and is regulated by the T7 promoter; T7 RNA polymerase is used to transcribe the target gene.[4] Due to termination inefficiency, read-through can result in increased regulation of downstream genes that may be crucial to host cell function.[4] Selectable marker genes that are downstream of the target gene insertion site and genes that encode regulatory proteins may have altered expression as a result.[4] Hence, proper termination of transcription is needed for plasmid stability in host cells for the proper production of recombinant proteins.[4] Research has been conducted to identify termination signals that yield higher termination efficiency by engineering termination signals from a variety of termination signal components.[4] Some engineered termination signals have yielded a termination efficiency as high as 99%, which is a significant improvement from the native termination efficiency associated with T7 RNA polymerase of 74%.[4]
Translation
[edit]In translation, termination efficiency is dependent on the context of the termination signal (stop codon).[5] Traditionally, the termination signal for translation is a 3 nucleobase sequence called a stop codon.[5] Research has shown that the nucleobases surrounding the stop codon can impact termination efficiency.[5] Specifically, the 4th base (nucleobase directly following the stop codon) has a significant impact on the termination efficiency.[5] In particular, when the nucleobase at the 4th position is a purine (adenine or tyrosine), termination efficiency is improved.[5] Pyrimidines (guanine or cytosine) in the 4th position result in lower termination efficiency.[5] It has been found that highly expressed genes have higher termination efficiency due to the presence of a purine in the 4th position.[5]
References
[edit]- ^ a b c d Pelley, John W. (2012-01-01), Pelley, John W. (ed.), "16 - RNA Transcription and Control of Gene Expression", Elsevier's Integrated Review Biochemistry (Second Edition), Philadelphia: W.B. Saunders, pp. 137–147, ISBN 978-0-323-07446-9, retrieved 2021-10-15
- ^ a b c d e f g h i j k l m n o Santangelo, Thomas; Artsimovitch, Irina (9 May 2011). "Termination and antitermination: RNA polymerase runs a stop sign". Nature Reviews Microbiology. 9: 319–329 – via PubMed.
- ^ McCaughan, K. K.; Brown, C. M.; Dalphin, M. E.; Berry, M. J.; Tate, W. P. (1995-06-06). "Translational termination efficiency in mammals is influenced by the base following the stop codon". Proceedings of the National Academy of Sciences. 92 (12): 5431–5435. doi:10.1073/pnas.92.12.5431. ISSN 0027-8424. PMID 7777525.
- ^ a b c d e f g h i Mairhofer, Juergen; Wittwer, Alexander; Cserjan-Puschmann, Monika; Striedner, Gerald (2015-03-20). "Preventing T7 RNA Polymerase Read-through Transcription—A Synthetic Termination Signal Capable of Improving Bioprocess Stability". ACS Synthetic Biology. 4 (3): 265–273. doi:10.1021/sb5000115.
- ^ a b c d e f g McCaughan, K. K.; Brown, C. M.; Dalphin, M. E.; Berry, M. J.; Tate, W. P. (1995-06-06). "Translational termination efficiency in mammals is influenced by the base following the stop codon". Proceedings of the National Academy of Sciences. 92 (12): 5431–5435. doi:10.1073/pnas.92.12.5431. ISSN 0027-8424. PMID 7777525.