Skip to main content
European Commission logo
English English
CORDIS - EU research results
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary
Content archived on 2024-06-18

Control of translation efficiency in proliferating and differentiated mammalian cells

Objective

Translation maps the transcriptome onto the proteome. It is regulated at the initiation levels and also by mRNA secondary structure, and – our current focus – by the interplay between the mRNA and tRNA pools. Although a lot is known about the mechanics of translation, its effects on physiology, particularly on proliferation and differentiation in mammals presents major open questions.
tRNAProlif offers an approach that consists of genome-wide measurements and analyses of the tRNA and mRNAs pools, and the interplay between them, in proliferative and differentiated cells. The project will explain how changes in translation affect, and are affected by, these two states.
We rely on our preliminary results that show a striking dichotomy in codon usage: genes involved in cellular proliferation have distinct codon usage compared to genes involved in differentiation and other multi-cellular process. Further, the tRNA pool consists of two distinct sub-populations: tRNAs whose codons are enriched among the proliferation genes are induced in proliferation and cancer, and tRNAs whose codons are enriched in differentiation genes are repressed in proliferation and are induced in differentiation. Towards understanding this “tRNA Switch” we aim at:
Causality: We will determine whether the tRNA pool affects the proliferation/differentiation status of cell. Conversely, we will determine the effects of the proliferation/differentiation status on the tRNA pool.
Regulation: We will establish the regulatory scheme that governs the “tRNA Switch”: we will determine the effects of transcriptional and post-transcriptional regulation on the tRNAs, depending on cell state. We will determine how the balance between the two tRNA sub-populations affects the proteome.
Evolution: We will conduct comparative genomics of regulation of tRNA availability and codon usage and its effect on physiology in multiple species.

Call for proposal

ERC-2013-CoG
See other projects for this call

Host institution

WEIZMANN INSTITUTE OF SCIENCE
EU contribution
€ 1 540 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

See on map

Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gabi Bernstein (Ms.)
Principal investigator
Yitzhak Pilpel (Prof.)
Links
Total cost
No data

Beneficiaries (1)