Updating our view of TIR
Sometimes results are sending you back to the drawing bord. It turns out that the auxin receptor TIR produces the second messenger cAMP. Now researchers led by Jiří Friml show in Nature that the production of cAMP and not the degradation of Aux/IAA proteins is the key to the activation of ARF transcription factors.
About twenty years long researchers lived in the assumption that after perceiving auxin the auxin receptor TIR the Aux/IAA proteins labels for degradation. And that this relieved the blocking effect that Aux/IAA proteins have on ARF transcription factors. Enabling ARF to activate auxin response genes. But then suddenly was there the fact that TIR after perceiving auxin also produce cAMP. Resulting in the question what is this cAMP doing?
First the researchers checked if the production of cAMP was needed for the degradation of Aux/IAA. This it turned out was not the case. TIR receptors who can’t produce ant cAMP, still label Aux/IAA for degradation.
Aux/IAA is not sitting on ARF to block its function
Subsequently the researchers studied what happens when TIR can no longer label Aux/IAA proteins. Stable Aux/IAA proteins prevented TIR from producing cAMP. The interaction with Aux/IAA was therefore needed for cAMP production.
In order to figure what cAMP does, the researchers analysed the gene activation in response to auxin. Finding that auxin regulated genes were not activated in plants with a TIR receptor that can’t produce any cAMP.
But the real test came when the researchers decoupled the cAMP production from TIR. When cAMP is produced in close proximity of the ARF gene activators, then ARF becomes active. Also, when no auxin was nearby, and no degradation of Aux/IAA proteins took place.
This shows that Aux/IAA is not sitting on ARF to block its function. But rather to lure TIR towards ARF, to produce cAMP in its vicinity, so that, in an up till now unknow way, it activates ARF. This study also asks researchers to look with new eyes how other similar signalling and gene activation pathways work.
Literature
Chen, H., Qi, L., Zou, M. et al. TIR1-produced cAMP as a second messenger in transcriptional auxin signalling. Nature (2025). https://doi.org/10.1038/s41586-025-08669-w
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