Editing Terminator (genetics) (section)

==In prokaryotes==
{{missing information|section|archaea, which has a more relaxed intrinsic ("rho-indep") requirement; archaeal FttA ({{PMID|33112729}})|date=December 2023}}
[[File:Prokaryotic terminators-en.svg|thumb|Simplified schematics of the mechanisms of prokaryotic transcriptional termination. In Rho-independent termination, a terminating hairpin forms on the nascent mRNA interacting with the NusA protein to stimulate release of the transcript from the RNA polymerase complex (top). In Rho-dependent termination, the Rho protein binds at the upstream rut site, translocates down the mRNA, and interacts with the RNA polymerase complex to stimulate release of the transcript.]]
Two classes of transcription terminators, Rho-dependent and Rho-independent, have been identified throughout [[prokaryotes|prokaryotic]] genomes. These widely distributed sequences are responsible for triggering the end of transcription upon normal completion of gene or [[operon]] transcription, mediating early termination of transcripts as a means of regulation such as that observed in [[attenuator (genetics)|transcriptional attenuation]], and to ensure the termination of runaway transcriptional complexes that manage to escape earlier terminators by chance, which prevents unnecessary energy expenditure for the cell.

===Rho-dependent terminators===
Rho-dependent transcription terminators require a large protein called a [[Rho factor]] which exhibits RNA [[helicase]] activity to disrupt the mRNA-DNA-RNA polymerase transcriptional complex. Rho-dependent terminators are found in [[bacteria]] and [[phage|phages]]. The Rho-dependent terminator occurs downstream of translational [[stop codon]]s and consists of an unstructured, cytosine-rich sequence on the mRNA known as a [[Rho utilisation site|Rho utilization site]] (''rut''),<ref>{{cite journal |last1=Di Salvo |first1=Marco |last2=Puccio |first2=Simone |last3=Peano |first3=Clelia |last4=Lacour |first4=Stephan |last5=Alifano |first5=Pietro |title=RhoTermPredict: an algorithm for predicting Rho-dependent transcription terminators based on Escherichia coli, Bacillus subtilis and Salmonella enterica databases |journal=BMC Bioinformatics |date=7 March 2019 |volume=20 |issue=1 |page=117 |doi=10.1186/s12859-019-2704-x |pmid=30845912 |pmc=6407284 |doi-access=free}}</ref> and a downstream transcription stop point (''tsp''). The ''rut'' serves as a mRNA loading site and as an activator for Rho; activation enables Rho to efficiently hydrolyze [[Adenosine triphosphate|ATP]] and translocate down the mRNA while it maintains contact with the rut site. Rho is able to catch up with the RNA polymerase because it is being stalled at the downstream ''tsp'' sites. Multiple different sequences can function as a tsp site.<ref name="Richardson1996">{{cite journal|last1=Richardson|first1=J. P.|title=Rho-dependent Termination of Transcription Is Governed Primarily by the Upstream Rho Utilization (rut) Sequences of a Terminator|journal=Journal of Biological Chemistry|volume=271|issue=35|year=1996|pages=21597–21603|issn=0021-9258|doi=10.1074/jbc.271.35.21597|pmid=8702947|doi-access=free}}</ref> Contact between Rho and the RNA polymerase complex stimulates dissociation of the transcriptional complex through a mechanism involving [[allosteric regulation|allosteric effects]] of Rho on RNA polymerase.<ref name="Ciampi-2006">{{Cite journal  | last1 = Ciampi | first1 = MS. | title = Rho-dependent terminators and transcription termination | journal = Microbiology | volume = 152 | issue = Pt 9 | pages = 2515–28 |date=Sep 2006 | doi = 10.1099/mic.0.28982-0 | pmid = 16946247 | doi-access = free }}</ref><ref>{{cite journal|last=Epshtein|first=V|author2=Dutta, D |author3=Wade, J |author4= Nudler, E |title=An allosteric mechanism of Rho-dependent transcription termination.|journal=Nature|date=Jan 14, 2010|volume=463|issue=7278|pages=245–9|pmid=20075920|doi=10.1038/nature08669 |pmc=2929367|bibcode=2010Natur.463..245E}}</ref>

===Rho-independent terminators===
{{main|Intrinsic termination}}
[[Intrinsic termination|Intrinsic transcription terminators]] or Rho-independent terminators require the formation of a [[Nucleic acid thermodynamics|self-annealing]] [[Hairpin (genetics)|hairpin]] structure on the elongating transcript, which results in the disruption of the [[polymerase|mRNA-DNA-RNA polymerase ternary complex]]. The terminator sequence in DNA contains a 20 basepair GC-rich region of [[dyad symmetry]] followed by a short poly-A tract or "A stretch" which is transcribed to form the terminating hairpin and a 7–9 nucleotide "U tract" respectively. The mechanism of termination is hypothesized to occur through a combination of direct promotion of dissociation through [[allosteric regulation|allosteric effects]] of hairpin binding interactions with the RNA polymerase and "competitive kinetics".  The hairpin formation causes RNA polymerase stalling and destabilization, leading to a greater likelihood that dissociation of the complex will occur at that location due to increased time spent paused at that site and reduced stability of the complex.<ref name="von Hippel1998">{{cite journal|last1=von Hippel|first1=P. H.|title=An Integrated Model of the Transcription Complex in Elongation, Termination, and Editing|journal=Science|volume=281|issue=5377|year=1998|pages=660–665|doi=10.1126/science.281.5377.660|pmid=9685251|bibcode=1998Sci...281..660.|s2cid=11046390}}</ref><ref name="GusarovNudler1999">{{cite journal|last1=Gusarov|first1=Ivan|last2=Nudler|first2=Evgeny|title=The Mechanism of Intrinsic Transcription Termination|journal=Molecular Cell|volume=3|issue=4|year=1999|pages=495–504|issn=1097-2765|doi=10.1016/S1097-2765(00)80477-3|pmid=10230402|doi-access=free}}</ref>
Additionally, the elongation protein factor NusA interacts with the RNA polymerase and the hairpin structure to stimulate transcriptional termination.<ref name="Santangelo-2011">{{Cite journal  | last1 = Santangelo | first1 = TJ. | last2 = Artsimovitch | first2 = I. | title = Termination and antitermination: RNA polymerase runs a stop sign. | journal = Nat Rev Microbiol | volume = 9 | issue = 5 | pages = 319–29 |date=May 2011 | doi = 10.1038/nrmicro2560 | pmid = 21478900 | pmc=3125153}}</ref>