tmRNA

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tmRNA is short for transfer messenger RNA . It is a small, stable ribonucleic acid ( RNA for short ). The name is a combination of tRNA ( transfer RNA ) and mRNA ( messenger RNA ). It is named after the ability to combine properties of both types of RNA. Other, but outdated, common names are 10S RNA and 10Sa RNA .

Occurrence

Genes for tmRNA have been found in every bacterial genome , including bacteria with significantly reduced genetic makeup. In contrast, tmRNA was not identified in archaea or - with the exception of some organelles - in eukaryotes .

gene

The gene that codes for tmRNA is called ssrA . It is synthesized as other tRNAs from a Vorläufertranskript and also in a similar manner by ribonucleases further processed, for example by RNase P or RNase E . Bacteria that subsequently introduce the CCA sequence at the 5 'end (post-transcriptional) do the same for their pre-tmRNAs. This happens, for example, in Bacillus subtilis .

The protein SmpB, which is essential for the function of the tmRNA, is encoded by the smpB gene.

In most bacterial species, tmRNA is not essential, but can lead to growth defects, for example after stress responses. For Neisseria gonorrhoeae , Shigella flexneri , Mycoplasma genitalium or Haemophilus influenzae , however, the activity of the tmRNA is essential for survival.

construction

Comparison between a tRNA, an mRNA and a tmRNA (right).

The tRNA part of the tmRNA has both a TΨC strain and an acceptor strain that ends with the tRNA-typical sequence CCA-5 '. But the anticodon stem and the D loop are missing. A special open reading frame (ORF) is similar to an mRNA and codes for a protein sequence that is later attached to an existing protein (see also section Function). Three to four pseudoknots were also identified in tmRNA , the exact function of which is still unclear.

The tRNA structural elements of the tmRNA correspond to those of a tRNA that alanine recognizes (tRNA Ala ). The acceptor strain contains the special G • C Wobbel base pair , which is crucial for recognition by the alanine tRNA synthetase . As a result, the tmRNA is loaded with alanine by this alanine tRNA synthetase.

The anticodon strain is essential for the function of a normal tRNA. In the tmRNA this is replaced by a special protein: SmpB. It has to bind to the tmRNA so that it can fulfill its function. A structure of the tRNA-like domain of the tmRNA was identified in a complex with the SmpB protein.

Working method

Due to its shape, the tmRNA, like a tRNA, is able to dock on a ribosome in the waiting state (English stalled ribosome ) and thus resume the translation process. Here the own mRNA part of the tmRNA is used as the new reading frame. The translation process is now continued with this, which is also known as trans translation. As a result, the previously produced peptide chain is extended by a special marking in the form of a peptide chain residue. This rest serves as a signal for later degradation. A stop codon on the mRNA part ends the translation and thus the release of the ribosome.

Functions

Quality control

During the translation of mRNA on ribosomes into proteins , it can happen that the mRNA lacks a stop codon . This happens, for example, because the transcription of the mRNA was terminated prematurely before the stop codon was reached. A reading frame shift can also lead to a stop codon no longer occurring in the reading frame. Alternatively, the stop codon occurring in the mRNA can be skipped during translation. In all of these examples, the ribosome finally reaches the 3 'end of the mRNA and remains in this waiting state; it can neither “back” in the 5 'nor “forward” in the 3' direction.

Since this complex of ribosome and mRNA is stable in the cellular environment, these ribosomes are withdrawn from the translation pool and remain useless in the cytosol. In Escherichia coli, such a faulty translation occurs up to 13,000 times per cell division, and on average every ribosome in the cell is affected during a cell cycle.

In addition, the proteins and peptides produced and possibly released in the process do not fulfill any task because they have not reached their full length. They can also be potentially harmful to the cell .

To counter this, the tmRNA fulfills the following important functions:

  1. It frees stuck ribosomes from the mRNA and adds them back to the translation pool.
  2. It marks the incomplete peptide chains produced during translation for degradation.

Regulation of gene expression

In addition to its quality control task, trans translation also plays an important role in the regulation of gene expression in some substrates.

In E. coli , trans translation is used to regulate LacI. LacI is the homotetrameric repressor of the lac operon , which - if sufficient glucose is available - binds to the promoter sites of the lac operon. This prevents the lacZ , lacY and lacA genes from being read , which would be necessary for the breakdown of lactose . The LacI repressor autoinhibits its own synthesis; it binds to two lac operator sites, O 1 and O 3 . O 1 lies with the lacZYA promoter, O 3 at the end of the coding region for lacI itself. When LacI binds to O 1 and O 3 , a loop is formed for the DNA in between . If an RNA polymerase now reads the lacI gene ( transcription ), it arrives at this loop before reaching the stop codon and falls off. The transcribed LacI is thus incomplete, among other things the stop codon is missing.

Ribosomes reading this incomplete LacI mRNA would end up stuck at the 3 'end. Only through the process of the tmRNA in the trans translation is it ensured that these ribosomes are freed and the incomplete LacI (LacI *) is broken down. The latter is the decisive task in the regulation by the trans translation, because it has been shown that LacI * is still an active repressor; the regulation of gene expression would fail without the process of trans translation.

Another example of the role of trans translation is proposed in the context of a stress response. Under stress conditions, the toxin RelE causes a global, cellular translation stop by cutting mRNAs. This is to ensure that valuable resources are immediately diverted to essential cellular processes - translation is an expensive process. When the stress inducing cause has been overcome, RelE is inactivated. The process of trans translation frees the ribosomes so that the cell can work normally again.

Individual evidence

  1. ↑ a b K. C. Keiler: Biology of trans-translation. In: Annu Rev Microbiol. 62, 2008, pp. 133-151. PMID 18557701 . doi: 10.1146 / annurev.micro.62.081307.162948 .
  2. ↑ Y. Bessho et al .: Structural basis for functional mimicry of long-variable-arm tRNA by transfer-messenger RNA . In: Proc. Natl. Acad. Sci. USA . tape 104 , no. 20 , 2007, p. 8293-8298 , doi : 10.1073 / pnas.0700402104 , PMID 17488812 .
  3. ↑ T. Abo et al .: SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon. In: EMBO J. 19 (14), 2000, pp. 3762-3769. PMID 10899129 . PMC 313975 (free full text, PDF).
  4. ↑ SK Christensen, K. Gerdes: RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. In: Mol Microbiol. 48 (5), 2003, pp. 1389-1400. PMID 12787364 .

literature

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