Valentin BEAUVAIS, PhD student in the "DAIH Team: Dysregulation of Authophay in Inflammation Due to HIV", will defend his thesis on Wednesday July 5, 2023 at 2:00 p.m. at the Charles Auditorium, CNRS Campus in Orléans.

Download the thesis defense notice (the link will be activated soon)

Abstract:

The transcription of messenger RNA (mRNA) is a complex process implicating a large diversity of players at very specific steps. The production of an mRNA also requires its maturation into a ribonucleoproteic particle (mRNP) through the binding of proteins that will package, protect and allow the mRNP to be exported to the cytoplasm where it will be translated into a protein. This crucial step is monitored by a quality control system (QC) that detects the rare aberrant mRNPs and induces their degradation by one of the exosome-dependent exonuclease, Rrp6. The error rate during mRNA maturation is very low and complicates the study of the QC. The induction of the bacterial factor Rho leads to the formation of aberrant mRNPs while avoiding the deletion of any protein potentially implicated in the QC system. The present study focuses on the THO complex, a keystone for the maturation of mRNA as it binds to chromatin early during transcription and then serves as a recruitment platform for other packaging proteins. The use of genome-wide analysis techniques (ChIP-seq) revealed the implication of Tho2 for the detection of aberrant transcripts and their degradation by Rrp6, independently from the THO complex. Furthermore, a similar approach (RNA-seq) on Rrp6-depleted yeast highlighted once again the importance of ncRNA degradation for the regulation of coding gene expression. Finally, the expansion of Rho utilization from yeast to human could bring to light the implication of nuclear speckles in the quality control of mRNPs in humans.

Keywords :

mRNP biogenesis, HTS techniques, Rho, THO complex, Rrp6, Nuclear speckles