CE12 - Génétique, génomique et ARN

CHApiTRE : CHAracterization of piRNA cluster expression throughout development and their capacity to tame a sudden TRansposable Element activity – CHApiTRE

Submission summary

Eukaryotic genomes are mainly composed of repeated sequences including transposable elements (TEs), highly mutagenic mobile DNA sequences which constitute a serious threat for the genome integrity. These TEs reside in the genome of all species and represent almost half of the human genome. A fine control of TE expression is essential to avoid their mobilization and the emergence of pathologies, while taking advantage of their evolutionary advantages. The first level of TE control has to occur in the germline cells since the genetic information of these cells will be transmitted to the descendants. Ten years after the discovery of the first small non-coding RNAs (miRNAs, siRNAs), a third class of small RNAs, piRNAs (Piwi interacting RNA), was discovered in the germ line of all metazoans including human. These piRNAs, which do not encode any protein, appeared to be key regulators of the TE expression and a fine regulation of their expression is required to avoid the appearance of many pathologies. Despite the evolutionary distance which separates Drosophila from humans, a strong conservation of the molecular networks of the piRNA pathway has been demonstrated. Drosophila is therefore an excellent model for studying this pathway. These millions of piRNAs produced by germ cells come from particular genomic loci called piRNA clusters. The transcription of these clusters can be uni or dual-strand. piRNA clusters are composed of a multitude of TEs either full length or truncated that represent the repertoire of TEs that the cell must repress to maintain the genome stability. However, following a reactivation of TEs in somatic tissue adjacent to germ cells, some TEs are able to infect and invade the germ line genome as a virus would do. The initiation of uni-strand piRNA cluster expression during development as well as their evolution following a neo-invasion of TEs are still poorly understood. The proposed project will be organized into two complementary objectives. The objective (1) of our project is to study in vivo the initiation of uni-strand piRNA expression, and this in order to identify how the genomic repression of TEs takes place in the zygote. We will also study the characteristics of these non-coding piRNAs precursors, which distinguish them from others messenger RNAs to be matured into piRNAs by the cellular machinery. The objective (2) is to follow the impact of a TE neo-invasion from an adjacent somatic tissue towards the germ line. The response of the germ line and the establishment of adaptation mechanisms to ultimately allow the control of TE and the survival of the species will be studied. Combined imaging, genetics, genomics, genome editing (CRISPR) and bioinformatics approaches will be used to complete this project. Overall, the original questions that are addressed in this project will bring new insights on the function of this class of small RNAs in the initiation of TE silencing and on the maintenance of genomic stability but also on the evolutionary dynamics of TEs.

Project coordination

Emilie BRASSET (Génétique Reproduction et Développement)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

GReD Génétique Reproduction et Développement

Help of the ANR 328,752 euros
Beginning and duration of the scientific project: August 2021 - 48 Months

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