CE12 - Génétique, génomique et ARN

Protein-only RNase P as a central regulator of tRNA homeostasis in Arabidopsis nuclei – PROPHAN

Submission summary

Nuclear tRNAs are transcribed by RNA polymerase III and matured in 5’ by RNase P enzymes called PRORP2/3 in plants. The investigation of interaction networks of Arabidopsis nuclear PRORP2/3 has identified novel RNA substrates and protein partners. PRORP2/3 cleaves the mRNA of MAF1, a main regulator of RNA polymerase III, at the level of a conserved tRNA-like structure and thus regulates MAF1 mRNA level in vivo. This led to the hypothesis that PRORP2/3 indirectly regulate RNA polymerase III activity. Moreover, PRORP2/3 were found to be the main interactants of TRM1A/B, a group of enzymes that add a m2,2G modification on residue 26 of tRNAs. The analysis of TRM1 mutants revealed that the pool of tRNAs is considerably modified in TRM1 mutants. This led to the hypothesis that the PRORP2/3-TRM1 complex might be involved in the regulation of tRNA homeostasis in plant cells. Interestingly, TRM1 was previously shown to be functionally linked to RNA polymerase III activity in yeast. Altogether, preliminary results point out two novel, possibly interconnected, pathways involving PRORP2/3 that appears to regulate the pool of tRNAs.
This project proposes to investigate in depth these two regulatory pathways at the functional and mechanistic levels and to explore how the two pathways are interconnected. The project, proposed by the team of P. Giegé, a recognized expert in tRNA biology, will be multi-disciplinary. It will rely on a combination of complementary approaches including reverse genetics, molecular biology, i.e. NGS approaches, biochemistry and structural biology i.e. cryo-electron microscopy. All these methodologies have been successfully used by the team.
Overall, the project will reveal how novel pathways contribute to the regulation of the pool of tRNAs and how this in turns impacts translation. In a broader context, this project will contribute to unravel the diversity of translation regulation processes across eukaryotes.

Project coordination

Philippe GIEGÉ (Centre national de la recherche scientifique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IBMP Centre national de la recherche scientifique

Help of the ANR 307,405 euros
Beginning and duration of the scientific project: November 2022 - 48 Months

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