Cis- and trans-acting regulations of mRNA biogenesis and their impact on genetic stability

Establishment of gene expression patterns requires the regulated transcription of mRNAs, a process which will expose the genetic material to potentially harmful agents and come into conflict with genome duplication. Nonetheless, genome integrity has to be maintained over generations without accumulation of deleterious mutations. Coordination of these distinct DNA-dependent transactions is therefore required to ensure genome homeostasis. In this respect, mRNAs packaging into mRNPs (messenger ribonucleoparticles) involves the recruitment of a battery of proteins controlling mRNA fate, but also counteracting the formation of genotoxic mRNA::DNA hybrids (or R-loops) between the nascent mRNA and its DNA template. We are investigating the cis- and trans-acting regulations that target mRNP biogenesis and their impact on gene expression and genetic stability in budding yeast. In this frame, we have more particularly explored (i) the rôle of SUMOylation events in the regulation of mRNP assembly and (ii) the importance of intronic sequences in the maintenance of genomic stability.