tmRNA (also known as 10Sa RNA) stands for transfer-messenger-RNA. The gene encoding the tmRNA is ssrA. It is found in all bacterial genomes that have been sequenced, and is an important part of translation regulation. To remain stable, tmRNA associates with Small Protein B (SmpB).
The purpose of tmRNA is three-fold:
1. To rescue stalled ribosomes
- the ribosomes are stuck on incomplete, or "nonstop", mRNA's (messenger RNA).
- stop codons also act as a binding site for release factors, so with no stop codon, the ribosome is literally stuck
- stalled ribosomes occur about 13,000 times during a cell's life time (E.coli), so it is important to not leave ribosomes stuck on the mRNAs
2. To tag the incomplete polypeptide chains
- the peptides are products of incomplete mRNA sequences, and therefore are probably wrong. Improperly folded proteins could be very dangerous to a cell
3. To promote the degradation of the abberrant mRNA
- has just recently been shown to do this.
- it is been hypothesized that RNaseR is involved with this function because it has been found to complex with tmRNA and SmpB.
Ways to get "nonstop" mRNA are early transcriptional termination, partial degradation of the mRNA, and readthrough of inframe stop codons. Since there are no stop codons, there are no release factors. The ribosome will just sit idly on the mRNA until tmRNA or another system rescues it. It is unclear how the tmRNA-SmpB complex recognizes stalled ribosomes. To rescue the stalled ribosome, the tmRNA first behaves similarly to tRNA in that it inserts itself into the A-site of the ribosome. Then the tmRNA behaves like mRNA, and provides the ribosome with a template.
The tRNA portion of the tmRNA has a D-loop (but no stem) and a T-stem. It also has an acceptor arm that accepts an alanine. The structure has the minimum requirements for alanine-tRNA synthetase to recognize it and put an alanine on the acceptor stem. Instead of the anti-codon region, the tmRNA has an open reading frame that encodes for the peptide tag. It also has four pseudoknots, although the exact purpose of them is still unclear. SmpB is thought to associate with the D-loop. A structure of the tRNA-like domain of tmRNA has been solved in complex with the SmpB protein.