What is it about?

Transcription–translation coupling refers to when translation initiates during mRNA transcription. While beneficial at most genes, this phenomenon constrains tight gene repression. At many type I toxin genes, cotranscriptional translation is bypassed by a two-step mechanism. First, intramolecular structure renders the nascent mRNA translationally inactive, while subsequent ribonucleolytic processing generates an active mRNA. Second, the active mRNA is silenced by an antisense small RNA (sRNA). Contrary to this established mechanism, we here suggest an alternative mechanism for bypassing cotranscriptional translation. Instead of ribonucleolytic processing, the nascent timP mRNA is activated through a structural transition, which involves the formation of a pseudoknot. The active mRNA is specifically targeted by the sRNA TimR, which destabilizes the pseudoknot to inhibit translation.

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Why is it important?

This work suggests a new mechanism by which a translationally inactive mRNA can gain activation through a conformational change in the mRNA. The structural transition involves the formation of an RNA pseudoknot fold which is essential for translation to initiate.

Perspectives

We hope that this work will increase the interest in non-canonical mechanisms of translation initiation and the importance of mRNA folding in this process.

Erik Holmqvist
Uppsala Universitet

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This page is a summary of: An RNA pseudoknot mediates toxin translation and antitoxin inhibition, Proceedings of the National Academy of Sciences, June 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2403063121.
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