Non-stop decay

[3] Non-stop decay (NSD) is a cellular pathway that identifies and degrades aberrant mRNA transcripts that do not contain a proper stop codon.

The NSD mechanism requires the interaction of RNA exosome with the Ski complex, a multi-protein structure that includes the Ski2p helicase and (notably) Ski7p.

The short splicing isoform of HBS1L (HBS1LV3) was found to be the long-sought after human homologue of Ski7p, linking the exosome and SKI complexes.

Together, Hbs1/Dom34 are capable of binding to the 3’ end of an mis-regulated mRNA, facilitating the dissociation of malfunctioning or inactive ribosomes in order to restart the process of translation.

In bacteria, trans-translation, a highly conserved mechanism, acts as a direct counter to the accumulation of non-stop RNA, inducing decay and liberating the misregulated ribosome.

[4] Once bound, SmpB engages in a transpeptidation reaction with the improperly functioning polypeptide chain through the donation of charged alanine.

[4] The modified portion of RNA, along with the amino acid tag, are translated, and demonstrate incomplete characteristics, alerting and allowing for intracellular proteases to remove these harmful protein fragments, causing stalled ribosomes on damaged mRNA to resume function.