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teachingWe are always keen to hear from candidates with an interest in DNA methylation, noncoding RNA and nuclear architecture.

Ph.D students and Postdocs fellows interested in joining the laboratory should send us a cover letter, a full CV and the names of three referees in order to study national and international solutions for fellowships.

Send all requests to Claire Francastel

 


M2 Proposal (1)
Identification of new regulatory RNAs that originate from alternative splicing of introns

The current vision of the RNA world, which distinguishes between coding and non-protein-coding RNAs (ncRNA), has recently been questioned with the demonstration that some RNAs could function both as mRNAs in the production of proteins and as inherently functional ncRNAs. We focus on a class of RNAs for which this duality is influenced by alternative splicing of small introns and dictates the fate of human progenitors. Beyond this duality, introns also represent a fraction of the transcriptome to which different regulatory functions have been assigned including release of small regulatory RNAs such as miRNA; the mirtron pathway produces pre-miRNA-like hairpin structures after debranching of the intron-lariat produced by splicing. Using computational and experimental approaches we have identified, in the human genome, new candidate mirtrons and bifunctional RNAs, i.e. in which disruption of the ORF by intron retention potentially generates a cognate ncRNA. These findings open up a whole new field of investigation in which questioning the type of molecule produced by a given genetic entity, and the factors that influence their biogenesis, becomes critical. Current challenges now consist in documenting the functional diversity generated by alternative splicing that is likely to unveil original aspects of transcriptional circuitries that govern stem cell fate.

  • We will use Next Generation Sequencing to systematically identify novel multifunctional transcripts, including intron retaining non-coding isoforms and their cognate mRNA, and stable introns holding the potential to produce regulatory small RNAs, in the context of muscle stem cells. A bioinformatian (postdoc) is already working in the team.
  • We will use bioinformatics tools to analyze these datasets and identify new small regulatory RNAs.
  • We will experimentally validate these data by classical northern blot assays or stem-loop-PCR to detect introns and their associated small RNA in the context of muscle stem cells.

Reading:

  • Hubé F, Ulveling D, Sureau A, Forveille S, Francastel C. Short intron-derived ncRNAs. Nucleic Acids Res. 2017;45(8):4768-4781. -Hubé F, Francastel C. Mammalian introns: when the junk generates molecular diversity. Int J Mol Sci. 2015;16(3):4429-52.
  • Francastel C, Hubé F. Coding or non-coding: Need they be exclusive? Biochimie. 2011;93(11):vi-vii.
  • Ulveling D, Francastel C, Hubé F. Identification of potentially new bifunctional RNA based on genome-wide data-mining of alternative splicing events. Biochimie. 2011;93(11):2024-7.
  • Ulveling D, Francastel C, Hubé F. When one is better than two: RNA with dual functions. Biochimie. 2011;93(4):633-44.
  • Hubé F, Velasco G, Rollin J, Furling D, Francastel C. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Nucleic Acids Res. 2011;39(2):513-25.

Send all requests to Florent Hubé or to Claire Francastel


M2 Proposal (2)
Identification Une solution logicielle pour catégoriser les petits ARN non codants

Nous venons d’identifier une nouvelle source de production de petits ARN non codants régulateurs issus de l’épissage d’introns. Afin de les caractériser et de les catégoriser, un nouvel outil est nécessaire.

Il existe plusieurs serveurs web ou solutions logicielles permettant de détecter la présence d’un pre-miARN dans une séquence génomique. De même, les solutions pour identifier un ARNt ou un snoARN existent depuis plus de 10 ans, et malgré les découvertes récentes de nombreuses nouvelles séquences, et de caractéristiques particulières et spécifiques à chacun, aucun nouveau système d’identification n’a vu le jour. Enfin, aucune de ces solutions n’indiquent quelles sont les “chances” d’avoir un miARN plutôt qu’un snoARN. C’est pourquoi, nous souhaiterions développer une solution “tout-en-un”, reprenant les caractéristiques récentes de chaque petits ARN non codants, de les “scorer”, et de permettre une identification fiable de chacun d’entre eux. Il s’agira donc de récupérer les informations de la littérature, de classifier et pondérer les différents critères retenus, et de programmer (à l’aide de script ou programme déjà écrit sur le web) un logiciel complet et efficace. Des jeux de données connues (miRBase, snoRNAbase, etc…) serviront de jeux de tests.

Send all requests to Florent Hubé or to Claire Francastel