Trans-translation in RNA

Study Notes

Trans-translation is a process where a tmRNA (transfer-messenger RNA) molecule is used, which is simultaneously a tRNA and an mRNA.
This process occurs when ribosomes stall, which can lead to a problem of producing a tail of stalled ribosomes, resulting in truncated proteins.
In eukaryotes, the solution to this problem is to remove the ribosome and eliminate the truncated proteins, and if the messenger is incorrect, degrade it.
In prokaryotes, the tmRNA molecule acts in place of the next aminoacyl-tRNA, freeing the stalled ribosome.
The tmRNA molecule has a tRNA-like structure at one end with an attached Ala, and a large extension with a tertiary structure and a reading frame marked in pink.
The tmRNA provides an alanine and a reading frame to continue, and the Ala binds the peptidyl to the tmRNA, causing the ribosome to shift.
This leads to the ribosome leaving the real mRNA and translating the pink side of the tmRNA, allowing normal tRNAs to enter.
The resulting proteins are tagged with Ala and the tmRNA sequence, which is a signal for proteolysis, similar to ubiquitin in eukaryotes.
The tmRNA competes and displaces the rest of the mRNA if the stall is not caused by the end of the truncated messenger.

A more important response to amino acid scarcity is the stringent response, which occurs when cells detect a lack of amino acids.
Prokaryotes, such as E. coli, can synthesize their own amino acids but will stop producing them if they are present in the culture medium or environment.
When amino acids are absent, the cells change their metabolism to produce them, and if they are then removed, the cells will respond by restricting growth and protein synthesis.
This response is triggered by alarmone molecules, which are derived from nucleotides and have a phosphate group at the 5' and 3' ends.
Alarmone molecules are unstable and have a short half-life, ensuring that the response is temporary and only active while the signal is present.
The absence of amino acids leads to tRNAs without amino acids, which can form a complex with EF-Tu, but not with aminoacyl-tRNAs.
This complex activates the RelA enzyme, which produces alarmone molecules and triggers the stringent response.
The stringent response reduces the synthesis of rRNA, tRNA, and mRNA, and increases proteolysis to generate amino acids.