When transfer‐messenger RNA scars reveal its ancient origins

Abstract

In bacteria, trans‐translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. This key process is universally conserved and plays a crucial role in the viability and virulence of all bacteria. It is performed by transfer‐messenger RNA (tmRNA) and its protein partner small protein B (SmpB). Here, we show that tmRNA is a key molecule that could have given birth to modern protein synthesis. The traces of an ancient RNA world persist in the structure of modern tmRNA, suggesting its old origins. Therefore, since it has both tRNA and mRNA functions, tmRNA could be the missing link that allowed modern genetic code to be read by the ribosome.

Rescuing stalled mammalian mitoribosomes – what can we learn from bacteria?

“…Trans-translation is the primary pathway for bacteria to rescue stalled ribosomes (reviewed in Keiler and Feaga, 2014). This process is mediated by an RNA species that resembles both a tRNA and an mRNA, hence being termed a tmRNA, as recently reviewed in detail (Guyomar and Gillet, 2019). Essentially, the 3′-terminus of the tRNA-like component of tmRNA ends in CCA that is charged by alanyl-tRNA synthetase (Komine et al, 1994).…”

“…The small SsrAbinding protein (SmpB) binds to the D-loop of the tRNA domain, which, when delivered to a stalled ribosome, fills the empty A-site (Gutmann et al, 2003), such that the mRNA domain can facilitate resumption of elongation until the stop codon is reached, with a peptide extension tagged at the C-terminal of the aberrant polypeptide. As a consequence (1) the defective nonstop mRNA is ejected and subsequently degraded by RNases such as RNase R, and (2) the C-terminal extension acts as a degron, targeting the potentially toxic aberrant peptide for degradation by proteases such as the ATP-dependent unfoldase ClpXP (Gottesman et al, 1998;Wiegert and Schumann, 2001;Guyomar and Gillet, 2019).…”