Terminator (genetics)

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As a terminator or transcription terminator that portion is of a genetic sequence on the DNA referred to, of the end of a gene or operon selected, since it the end ( termination ) of the transcription leads.

During the transcription, this terminating sequence is also rewritten by RNA polymerases into the nucleotide sequence of the newly formed RNA strand. In this form, the base sequence of a terminator on the RNA transcript is then the signal - termination signal - for those processes which, either directly or with the help of additional factors - termination factors - lead to the transcription process being terminated.

Simplified schemes
- an intrinsic (above)
- a rho-dependent (below)
termination of the transcription (shown in black: RNA of the transcript)

Two classes of transcriptional terminators are known in prokaryotes :

  • Intrinsic - acting through direct RNA interaction
  • Rho factor dependent - indirectly effective via protein factors

The DNA sequence of an intrinsic terminator usually contains short sequences of (four to ten) G / C base pairs and a sequence of identical bases ( T or A ). Transcribed in RNA, these are often found downstream immediately after a stop codon , which closes a reading frame (ORF) that is open for translation of the transcript .

The DNA sequence of the longer recognition region for the termination factor ( ρ ) of a rho-dependent termination usually contains many G and few C bases; this binding site ( called rut ), which is C-rich in RNA , is located upstream at some distance from a stop codon and the termination site.

In eukaryotes , like humans, the processes of transcriptional termination are less well understood. Here, too, nucleotide sequences play a role as termination signals. These are recognized by various proteins that bind to them as termination factors. In a complex interplay, they lead to the pausing of the RNA synthesis, the release of the RNA transcript and the detachment of the RNA polymerase from the DNA template. In eukaryotic cells, these sub-processes are often separate processes with a time delay, with intermediate steps of RNA processing .

As antitermination proteins, RNAs or (intrinsic) are referred RNA structures that prevent transcription termination.

Rho-independent termination (intrinsic termination)

With this type of termination, a hairpin-shaped secondary structure develops in the RNA transcript. The reason for this hairpin structure lies in the special sequence of bases. In addition, there is often a U -rich area. For the optimal structure of an intrinsic terminator, the following regions are needed in the transcript:

Structural model of an intrinsic terminator in RNA (5 ′ → 3 ′)
  • Stem-forming GC-rich regions a and c (6-8 nucleotides)
  • Loop-forming region b (3–5 nucleotides)
  • Poly- uracil region d (3–8 nucleotides)

The two GC-rich regions a and c superimposed to form the so-called stem ( stem ) together. The intermediate region b formed the so-called loop ( loop ). The resulting hairpin structure ( hairpin ) causes a delay of the transcription process, as long as it remains. This is facilitated by a flexible protein with special pocket formation, NusA , which is bound to the RNA polymerase. The RNA hairpin structure also leads to an allosteric inhibition of nucleotide addition at the active center of the RNA polymerase. With the subsequent uracil series d , the transcriptional complex loses its stability.

According to current theory, the RNA / DNA hybrid is shortened and shifted asymmetrically as a result of the RNA hairpin; the weak bond via UA base pairing between RNA and DNA then allows the destabilization with which the transcript is released from the complex.

Rho-independent termination is also used in attenuation to regulate gene expression.

Rho-dependent termination

Structural model of a Rho factor dependent terminator in RNA

In the rho factor -dependent termination no destabilizing sequence elements in RNA are needed, because termination is the termination factor Rho catalyzes a hexameric protein complex. The destabilization of the transcriptional complex is the result of the helicase activity of the Rho factor. Rho recognizes C -rich (and G- poor) sections on the transcript. On the newly synthesized RNA strand, it binds to an approximately 70  nt long region ( rut ) which is upstream of the termination point. With ATPase activity, Rho then moves towards the 3 'end of the RNA.

Rho becomes a termination factor through its action as a helicase, which leads to a separation of the RNA / DNA hybrid. The result is a dissociation of the complex and thus the release of the RNA transcript.

Distinction

The terminator sequences in the DNA double strand are not the same as those on the RNA single strand of the transcript. Incidentally, both are to be distinguished from the stop codons on the mRNA , which lead to the termination of translation .

literature

  • Rolf Knippers: Molecular Genetics. 8th revised edition. Georg Thieme Verlag, Stuttgart 2001, ISBN 3-13-477008-3 .

Individual evidence

  1. ^ Y. C Carafa, E. Brody, C. Thermes: Prediction of rho-independent Escherichia coli transcription terminators • :: A statistical analysis of their RNA stem-loop structures . In: Journal of molecular biology , 216 (4), 1990, pp. 835-858.
  2. ↑ I. Artsimovitch, R. Landick: Interaction of a nascent RNA structure with RNA polymerase is required for hairpin-dependent transcriptional pausing but not for transcript release . In: Genes & Development , 12 (19), 1998, pp. 3110-3122, doi: 10.1101 / gad.12.19.3110
  3. ↑ X. Guo, A. Myasnikov, J. Chen, C. Crucifix, G. Papai, M. Takacs, P. Schultz, A. Weixlbaumer: Structural Basis for NusA Stabilized Transcriptional Pausing. In: Molecular Cell , 69 (5), March 2018, pp. 816-827.
  4. ↑ I. Toulokhonov, I. Artsimovitch, R. Landick: Allosteric control of RNA polymerase by a site did contacts nascent RNA hairpins. In: Science , 292 (5517), 2001, pp. 730-733.
  5. ^ V. Brendel, GH Hamm, EN Trifonov: Terminators of transcription with RNA polymerase from Escherichia coli: what they look like and how to find them . In: Journal of biomolecular structure & dynamics , 3 (4), 1986, pp. 705-723, PMID 3078109
  6. ^ PH von Hippel, TD Yager: Transcript elongation and termination are competitive kinetic processes . In: Proceedings of the National Academy of Sciences , 88 (6), 1991, pp. 2307-2311.
  7. ↑ KM Walstrom, JM Dozono, PH von Hippel: Kinetics of the RNA-DNA helicase activity of Escherichia coli transcription termination factor rho. 2. Processivity, ATP consumption, and RNA binding . In: Biochemistry , 36 (26), 1997, pp. 7993-8004, PMID 9201946
  8. ↑ DJ Jin, RR Burgess, JP Richardson, CA Gross: Termination efficiency at rho-dependent terminators depends on kinetic coupling between RNA polymerase and rho . In: Proceedings of the National Academy of Sciences , 89 (4), 1992, pp. 1453-1457.