SsrA

ssrA, also called tmRNA, is a bacterial RNA molecule encoded by the ssrA gene. It functions as a hybrid between transfer RNA and messenger RNA and serves as a key participant in trans-translation, a quality-control pathway that rescues ribosomes stalled on defective, truncated, or damaged mRNAs during protein synthesis.

In the rescue reaction, tmRNA, together with the protein SmpB, enters the ribosome at the stalled A site. The nascent polypeptide is transferred to the tmRNA, which provides a short open reading frame encoding a degradation tag. Translation then resumes on the tmRNA ORF, appending the tag to the incomplete polypeptide. The resulting product is typically targeted for proteolysis by bacterial proteases such as ClpXP, Lon, or ClpAP, and the ribosome is recycled.

Structure and partners: tmRNA contains a tRNA-like domain that can be aminoacylated and a distinct mRNA-like domain that carries the tag-encoding sequence. SmpB binds to tmRNA and, together with elongation factors such as EF-Tu, guides the tmRNA–SmpB unit into the ribosome and coordinates frame-shifting from the original mRNA to the tmRNA ORF.

Genetics and distribution: The ssrA gene is widespread among bacteria and is also found in chloroplasts and some mitochondria. tmRNA lengths are typically in the hundreds of nucleotides, commonly around 360–400 nt. The system contributes to cell fitness, especially under stress, by preventing prolonged ribosome stalling and reducing accumulation of damaged polypeptides.

Discovery and significance: Trans-translation was characterized in the 1990s, revealing a conserved bacterial quality-control mechanism with implications for antibiotic action and cellular proteostasis.