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Cis-natural antisense and the enhancement of mRNA translation

English title Cis-natural antisense and the enhancement of mRNA translation
Applicant Poirier Yves
Number 154471
Funding scheme Sinergia
Research institution Dépt de Biologie Moléculaire Végétale Faculté de Biologie et de Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Molecular Biology
Start/End 01.12.2014 - 30.11.2018
Approved amount 1'342'791.00
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Keywords (7)

ribonucleoprotein complex; cis-natural antisense; plant; RNA-binding protein; RNA structure; ribosome footprinting; translation

Lay Summary (French)

Lead
Le contrôle de l’expression des gènes est essentiel pour que les êtres vivants puissent se développer normalement et survivre dans leur milieu naturel. Ce contrôle peut se faire de différentes façons. Le projet de recherche a pour but d’étudier un nouveau mécanisme de régulation de l’expression des gènes qui a été découvert chez le riz.
Lay summary

Contenu et objectifs du travail de recherche.

Les protéines codées par les gènes sont synthétisées via la production d’ARNs sens. Cependant, en plus d’ ARNs sens, certains gènes produisent aussi des ARNs anti-sens, appelé cis-NATs. Normalement, l’appariement d’un ARN sens avec son cis-NAT forme un ARN double brin qui est rapidement dégradé, résultant en la diminution de la production de la protéine correspondante. Nous avons récemment découvert que le gène PHO1 de riz exprimait un cis-NAT et que ce dernier stimulait la production de la protéine PHO1 (au lieu de la réprimer). Le projet de recherche a pour but de comprendre comment ce cis-NAT peut stimuler la production de protéine. La région du cis-NAT responsable de la stimulation sera définie et sa structure sera déterminée afin de comprendre son mode de fonctionnement. Des outils de génomique et de bioinformatique seront utilisés pour identifier d’autres cis-NATs chez le riz et la plante Arabidopsis pouvant stimuler la synthèse de protéines. Des groupes de recherche de l’Université de Lausanne et Vienne, ainsi que de l’ETH-Zurich, combineront leurs expertises pour accomplir ces buts.

 

Contexte scientifique et social du projet de recherche

Ce projet relève essentiellement de la recherche fondamentale. Cependant, la meilleure compréhension des mécanismes impliqués dans la stimulation de l’expression des gènes par les ARNs anti-sens peuvent, à moyen- et à long-terme, déboucher sur le développement de nouveaux outils en médecine (pour des approches thérapeutiques) ou en biotechnologie (animale ou végétale).

Direct link to Lay Summary Last update: 14.07.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
An antisense noncoding RNA enhances translation via localised structural rearrangements of its cognate mRNA
Reis Rodrigo S, Deforges Jules, Schmidt Romy R, Schippers Jos H M, Poirier Yves (2021), An antisense noncoding RNA enhances translation via localised structural rearrangements of its cognate mRNA, in The Plant Cell, 10.
Modulation of Shoot Phosphate Level and Growth by PHOSPHATE1 Upstream Open Reading Frame
Reis Rodrigo S., Deforges Jules, Sokoloff Tatiana, Poirier Yves (2020), Modulation of Shoot Phosphate Level and Growth by PHOSPHATE1 Upstream Open Reading Frame, in Plant Physiology, 183(3), 1145-1156.
Critical Role of Transcript Cleavage in Arabidopsis RNA Polymerase II Transcriptional Elongation
Antosz Wojciech, Deforges Jules, Begcy Kevin, Bruckmann Astrid, Poirier Yves, Dresselhaus Thomas, Grasser Klaus D. (2020), Critical Role of Transcript Cleavage in Arabidopsis RNA Polymerase II Transcriptional Elongation, in The Plant Cell, 32(5), 1449-1463.
Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions
Deforges Jules, Reis Rodrigo S., Jacquet Philippe, Vuarambon Dominique Jacques, Poirier Yves (2019), Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions, in BMC Genomics, 20(1), 601-601.
Control of Cognate Sense mRNA Translation by cis-Natural Antisense RNAs
Deforges Jules, Reis Rodrigo S., Jacquet Philippe, Sheppard Shaoline, Gadekar Veerendra P., Hart-Smith Gene, Tanzer Andrea, Hofacker Ivo L., Iseli Christian, Xenarios Ioannis, Poirier Yves (2019), Control of Cognate Sense mRNA Translation by cis-Natural Antisense RNAs, in Plant Physiology, 180(1), 305-322.
Concerted expression of a cell cycle regulator and a metabolic enzyme from a bicistronic transcript in plants
Lorenzo-Orts Laura, Witthoeft Janika, Deforges Jules, Martinez Jacobo, Loubéry Sylvain, Placzek Aleksandra, Poirier Yves, Hothorn Ludwig A., Jaillais Yvon, Hothorn Michael (2019), Concerted expression of a cell cycle regulator and a metabolic enzyme from a bicistronic transcript in plants, in Nature Plants, 5(2), 184-193.

Collaboration

Group / person Country
Types of collaboration
Prof. Nenad Ban / ETHZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Gene Hart-Smith, University of New South Wales Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Ioannis Xenarios/Université de Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Abstract

In recent years, research has revealed that a large proportion of the genome in both plants and animals is transcribed, generating numerous non-coding RNAs. One important class of long (more than 200 nucleotides) non-coding RNAs is natural antisense transcripts (NATs), RNAs containing sequences that are complementary to coding sense mRNAs. NATs can be grouped into two categories, namely trans-NATs and cis-NATs, depending on whether the antisense RNAs are generated from different loci (trans) or from the opposing DNA strand at the same locus (cis). The majority of our current knowledge on the effects of NAT expression on target gene expression is for cis-NATs, and these have been shown to play important roles for normal development and physiology of plants and animals. While cis-NATs expression primarily results in the reduced expression of the associated sense mRNA through mechanisms affecting transcription, such as chromatin methylation, two exceptional cases of cis-NATs that result in the stimulation of translation of the cognate mRNA have been described in the last year, namely for the cis-NAT to the mouse Uchl1 gene and the rice PHO1;2 gene. The main goal of this research proposal is to specifically address the frequency and the mode of action of cis-NATs in controlling gene expression via translation enhancement (TE) in two model plants, namely Arabidopsis for dicots and rice for monocots. This research project takes advantages of the strengths and complementarities of the three participating group, namely the group of Yves Poirier (University of Lausanne), Wilhelm Gruissem (ETH-Zurich) and Ivo Hofacker (University of Vienna). Together, this consortium aims to reach a deeper understanding of cis-NATs acting as TE through the use of an array of complementary experimental strategies, including: mining of public and in-house transcriptomic and proteomic databases, as well as comparative analysis of total mRNA expression versus ribosome-associated mRNAs, to uncover new links between expression of cis-NATs and increased translation of the cognate sense mRNAs; precisely defining the structural elements within cis-NAT that are responsible for TE activity and using such features to screen plant genomes to identify novel cis-NATs with TE potential; developing a fast and reliable transient assay system to test and dissect TE from a number of cis-NATs; probing the mode of action of cis-NATs as TE using ribosome footprinting; and identifying proteins interacting with cis-NATPHO1;2 and assessing their role in TE. Altogether, this ambitious project aims to make key contributions to our understanding of the mechanisms implicated in the control of TE by cis-NATs and uncover the importance of such cis-NATs in the translational control of protein expression in plants.
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