CORDIS
EU research results

CORDIS

English EN
The role of tRNA processing and modifications in protein quality control.

The role of tRNA processing and modifications in protein quality control.

Objective

Translation of the genetic code into functional proteins is a fundamental biological process essential for cell survival and function. tRNAs are critical in this process because they recognize the codons on the messenger RNA and bring the cognate amino acid to the nascent peptide. To become functional, tRNAs undergo a series of processing steps and chemical modifications. Recently, my host group discovered that cells lacking wobble uridine modifications in the tRNA anticodon display translational slow down, a defect that triggers widespread protein aggregation in yeast and nematodes. These findings were the first to link tRNA metabolism to protein quality control and established tRNA metabolism as a novel layer in the regulation of protein homeostasis. However, the mechanisms underlying this phenomenon remain unknown.
My goal is to elucidate how tRNA processing and modifications regulate protein quality control, by integrating genetic, biochemical, transcriptomic, translatomic and proteomic approaches.
- First, I will identify tRNA biosynthesis genes that are critical for protein aggregation, by assessing global protein homeostasis in yeast cells lacking genes required for tRNA processing and modifications.
- Second, I will characterize transcriptome-wide translation by ribosome profiling to determine whether protein aggregation phenotypes are accompanied by translational defect. This will reveal which tRNA processing and modifications are essential for optimal co-translational protein folding.
- Finally, I will use yeast and nematode models of neurodegenerative diseases to test the functional importance of candidate steps of tRNA metabolism in disease-associated protein aggregation.
My project will comprehensively address the link between tRNA metabolism and protein homeostasis. In particular, it will bridge RNA and protein quality control pathways and shed mechanistic insights into neurodegenerative diseases that originate from tRNA dysfunction.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

UNIVERSITAET BERN

Address

Hochschulstrasse 6
3012 Bern

Switzerland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 112 951,40

Participants (1)

Sort alphabetically

Sort by EU Contribution

Expand all

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 46 509,40

Project information

Grant agreement ID: 746340

Status

Ongoing project

  • Start date

    1 September 2018

  • End date

    31 August 2020

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 170 764,95

  • EU contribution

    € 159 460,80

Coordinated by:

UNIVERSITAET BERN

Switzerland