Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing

All queued up for metabolite regulation

29 November 2018

Metabolites known as polyamines regulate levels of their own biosynthetic enzymes by creating traffic jams of ribosomes — the organelles responsible for producing proteins.

A team, including scientists from University College Cork, showed that this ribosomal bottleneck can occur along the gene transcript that encodes AZIN1, an enzyme that indirectly promotes the production of polyamines. This ‘queue’ of stalled ribosome then prompts the backed-up organelles to make a different protein at an upstream start signal. Consequently, the cell machinery produces less AZIN1, helping to reduce polyamine levels.

The researchers propose that this auto-regulation mechanism involving ribosome queuing could be widespread, affecting many crucial cellular processes. Furthermore, since polyamine metabolism is often dysregulated in cancer, the findings could help expose new therapeutic targets for drug development.

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References

1. Molecular Cell 70, 254–264 (2018). doi: 10.1016/j.molcel.2018.03.015