In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized transcript RNA that trigger processes which release the transcript RNA from the transcriptional complex. These processes include the direct interaction of the mRNA secondary structure with the complex and/or the indirect activities of recruited termination factors. Release of the transcriptional complex frees RNA polymerase and related transcriptional machinery to begin transcription of new mRNAs.
In prokaryotes
Two classes of transcription terminators, Rho-dependent and Rho-independent, have been identified throughout 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 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 phages. The Rho-dependent terminator occurs downstream of translational stop codons and consists of an unstructured, cytosine-rich sequence on the mRNA known as a Rho utilization site (rut), 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 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. Contact between Rho and the RNA polymerase complex stimulates dissociation of the transcriptional complex through a mechanism involving allosteric effects of Rho on RNA polymerase.
Rho-independent terminators
Intrinsic transcription terminators or Rho-independent terminators require the formation of a self-annealing hairpin structure on the elongating transcript, which results in the disruption of the 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 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. Additionally, the elongation protein factor NusA interacts with the RNA polymerase and the hairpin structure to stimulate transcriptional termination.
In Archaea Transcription termination in archaea is not explained by a single pathway. Current work supports a mixed picture in which some archaeal transcripts end mainly at short U rich sequence signals, whereas others require dedicated protein factors that cut the RNA or actively dismantle the transcription complex. Archaeal termination differs from the usual bacterial model, where a strong RNA hairpin often plays the main role. At the same time, it also resembles eukaryotic RNA 3′ end processing because it involves the conserved nuclease aCPSF1, also known in some studies as FttA.
Sequence driven termination One major archaeal termination route is guided by the sequence of the transcript itself. In many archaea, the main stop signal is a short run of uridines in the RNA. These U rich tracts can cause the archaeal RNA polymerase to stop and release the transcript without the prominent upstream stem-loop that characterizes many bacterial intrinsic terminators. Sequences around the U rich tract can still influence how strongly termination occurs but the uridine rich region is the core signal.
aCPSF1/FttA-dependent termination A second major pathway uses the conserved factor aCPSF1 (Archaeal Cleavage and Polyadenylation Specificity Factor), often referred to as FttA (Factor that terminates transcription in Archaea). These enzymes are found across all archaeal phyla and are homologous to the eukaryotic nuclease CPSF-73. Instead of depending solely on passive release at a U-rich tract, aCPSF1/FttA recognizes U rich terminator regions, cleaves the RNA near its 3′ end and actively promotes transcription termination.
Eta-dependent termination Some Euryarchaea also use a different factor dependent mechanism that relies on Eta (Euryarchaeal Termination Activity), an ATP-dependent helicase. Eta does not terminate transcription by cleaving the RNA. Instead, it acts directly on the transcription elongation complex and uses energy from ATP hydrolysis to disrupt that complex and release the nascent RNA. It also appears to be especially important for removing stalled or arrested transcription complexes that would otherwise remain on the template.
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