CNRS

Evolution of photosynthetic functions and Genome dynamics

Nom complet (en toutes lettres)
Evolution of photosynthetic functions and Genome dynamics - Laboratoire Biologie du Chloroplaste et Perception de la Lumière chez les Microalgues - UMR7141 CNRS SU
Adresse

75005 Paris
France

SFBI
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Third generation sequencing to investigate a novel type of RNA regulation.

Intron retention (IR) occurs when an intron is included in a mature mRNA. Previously regarded as a byproduct of faulty splicing, transcripts with retained introns are often rapidly degraded by a surveillance mechanism called nonsense-mediated decay (NMD). Our team discovered that numerous cell types make use of this mechanism by increasing the amount of transcripts with retained introns for degradation in blood cells (Cell, 2013) and in pluripotent stem cells (Nature, 2014). IR was also recently found to modulate tumour suppressor genes in many different cancers (Nature Genetics, 2015).

Impact systémique des petits ARN régulateurs

Acronyme ou nom de la structure
Nom complet (en toutes lettres)
Impact systémique des petits ARN régulateurs
Adresse

141 rue de la Cardonille

34396 Montpellier

France

Téléphone
04.34.35.99.36
Description (English)

MicroRNAs ("miRNAs") are small post-transcriptional regulators. The function of these small RNAs in animals has been well characterized at a molecular level, but their role is less well known at the macroscopic scale: how could miRNAs have any biological function if they repress most of their targets less than 2-fold (while inter-individual gene expression fluctuation typically exceeds 2-fold, and is buffered by homeostatic mechanisms)?
According to the current dogma, each miRNA regulates tens or hundreds of targets, yet several observations suggest miRNAs have a much weaker impact on animal biology. We recently proposed an alternative hypothesis: most identified "targets" are not repressed enough by the miRNA to yield physiological consequences; these genes would rather act as competitive inhibitors, preventing the miRNA from interacting with its few, real targets. The only difference between real targets and competitive inhibitors would be the sensitivity of their biological activity to the modest repression guided by miRNAs. Hence the role of miRNAs in integrated phenomena should be assessed using a systems biology approach.
We are now testing directly the new hypothesis, assessing several of its predictions. We aim at providing the first quantitative analysis of miRNA action in vivo and an improvement in miRNA target identification (taking into account the extent of predicted repression and the robustness of affected biological pathways).
More generally, we are proposing a new vision of gene regulation: a regulatory target is not simply a gene that is affected by a regulatory pathway; it is a gene that is affected enough by the pathway - the extent of a measured regulation needs to be confronted to the robustness of biological systems to fluctuations.
 

English keywords
microRNA, systems biology, pseudo-targets
SFBI
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M3

Acronyme ou nom de la structure
Nom complet (en toutes lettres)
Modélisation Moléculaire Mésoscopique
Adresse

Laboratoire Jean Perrin
Université Paris 6 CNRS UMR 8237
4 place Jussieu T32-33 4e, Case Courrier 114

75252 PARIS Cedex 05, France
France

Téléphone
+33 (0)1 44 27 47 12
Fax
+33 (0)1 44 27 47 16
Description (English)
Mesoscopic modelling of biopolymersMembers: Jean CognetOlivier Ameline.

Our objective is to develop a tool of modelling and simulation of nucleic acids (NA). The proposed approach consists in describing the conformation as a flexible beam, represented by a ribbon, by means of the theory of non-linear elasticity of beams.

The determination of the conformation of NA (DNA or RNA) is a challenge as great as that put by the conformation of proteins. Indeed, the current knowledge of the detailed conformations of NA is very low (5-10 % of the Protein Data Bank, PDB, the bank of all the known conformations of biological macromolecules). Nevertheless since 2000, we admit that the conformation of NA could be as rich and varied as that of the proteins, and that the part of the genome transcribed in ARN is of an order of magnitude greater than that of the proteins. Therefore, the conformational wealth of NA and the low level of current knowledge make difficult the bioinformatic approach, which consists in deducing a conformation from those already known. That is why the physical modelling of biomolecules is very important for NA and one of the major objectives of research in molecular modelling is the treatment of the various scales, atomic and mesoscopic (residues, several nucléotides) in a coherent and physical way.

We developed an approach of molecular modelling called Biopolymer Chain Elasticity (BCE). It is based on the observation that the sugar-phosphate chain of NA behaves at mesoscopic scales as a flexible beam. We recently finalized a protocol for the resolution of the conformation of DNA hairpins [1] (cf. banner above), with which we solved the structure of an aptamer anti-MUC1 [2] (cf. figure 1). The results are remarkable because the conformations correspond at the same time to a minimum at different scales : global, intermediate, and local, i.e. an energy minimum on the scale of the loop of several nucleotides, of the individual nucleotides in the loop, and atomic bonds [1, 2]. Our objective is to generalize this methodology for the hierarchical modelling of NA chains by using the theory of the non-linear elasticity of beams. We approach the problem on two scales: (I) that of the skeleton treated as a geometrical and mechanical object, and (II) that of the side chains, considered as stiff objects articulated around their attachment point onto the skeleton. From then on, a tool of simulation containing real active ribbons for the resolution of macromolecules is possible.

 

English keywords
Mesoscopic modelling of biopolymers
SFBI
Membre de la SFBI

ARTbio

Acronyme ou nom de la structure
Nom complet (en toutes lettres)
Accessible, Reproducible & Transparent Bioinformatics
Adresse

75005 Paris
France

Téléphone
+33144277005
English keywords
Galaxy, RNA-seq, single cell RNAseq, small RNAs, virus metagenomics, continuous integration, cloud computing
SFBI
Membre de la SFBI