- This article is about genetics. For other uses, see Terminator (disambiguation)
In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon on genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized mRNA that trigger processes to release the mRNA from the transcriptional complex which can be mediated by the direct activity of the mRNA secondary structure and/or by 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.
Terminators 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 genes or operons, mediating early termination of transcripts as a means of regulation such as that observed in transcriptional attenuation, and to ensuring the termination of runaway transcriptional complexes that manage to escape earlier terminators by chance which prevents unnecessary energy expenditure for the cell.
Rho-dependent transcription terminators require a protein called 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. 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 for Rho from which it can translocate down the mRNA toward the RNA polymerase and is able to catch up because the RNA polymerase stalls at the downstream tsp site . Contact between Rho and the RNA polymerase complex stimulates dissociation of the transcriptional complex through an unclear mechanism involving allosteric effects of Rho on RNA polymerase and Rho's helicase activity.
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 contains a GC-rich region of dyad symmetry followed by a short poly-T track or "T stretch" which are transcribed to RNA to form the terminating hairpin and a 7-9 nucleotide "U track" 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" where 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 an 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.
Terminators in eukaryotes
After transcription is completed, processed mRNA with 5’ CAP and 3’ poly A is cleaved with the help of CPSF and cleavage stimulation factor. However, residual RNA strand remains in RNA polymerase II. RNA polymerase II continues on transcribing this strand for several thousand more nucleotide. XRN2, a RNase, attaches to carboxyl terminal domain of RNA polymerase II. It degrades the uncapped RNA from 5’ to 3’ until it reaches the RNA pol II. Similar to rho-dependent termination, XRN2 could either push polymerase out of the DNA template or pull the template out of the RNA polymerase.
RNA polymerase normally is capable to transcribe DNA to single stranded mRNA at an efficient rate. However, once it reads the DNA template passing poly-A signals, a conformational change is induced. This change of conformation reduces RNA's processivity. In this case, termination is not completed but degradation of mRNA but through limiting RNA polymerase's capabilities.
- Ciampi, MS. (Sep 2006). "Rho-dependent terminators and transcription termination.". Microbiology 152 (Pt 9): 2515–28. doi:10.1099/mic.0.28982-0. PMID 16946247.
- von Hippel, P. H. (1998). "An Integrated Model of the Transcription Complex in Elongation, Termination, and Editing". Science 281 (5377): 660–665. doi:10.1126/science.281.5377.660.
- Gusarov, Ivan; Nudler, Evgeny (1999). "The Mechanism of Intrinsic Transcription Termination". Molecular Cell 3 (4): 495–504. doi:10.1016/S1097-2765(00)80477-3. ISSN 1097-2765.
- Santangelo, TJ.; Artsimovitch, I. (May 2011). "Termination and antitermination: RNA polymerase runs a stop sign.". Nat Rev Microbiol 9 (5): 319–29. doi:10.1038/nrmicro2560. PMID 21478900.
- Watson, J. (2008). Molecular Biology of the Gene. Cold Spring Harbor Laboratory Press. pp. 410–411. ISBN 978-0-8053-9592-1.
- Luo, W.; Bartley D. (2004). "A ribonucleolytic rat torpedoes RNA polymerase II.". Cell 119: 911–914. PMID 15620350.