Biogenesis and processing of functionally related mRNAs: from genome to proteome homeostasis

The co-transcriptional assembly of mRNAs into messenger ribonucleoparticles (mRNPs) is pivotal for both genome expression and integrity: indeed, the combinatorial association of RNA-binding proteins (RBPs) to mRNAs does not only define their cellular fate, but also counteracts the accumulation of genotoxic DNA:RNA hybrids, or R-loops. To further understand how these processes are coordinated, especially for functionally related mRNAs, we systematically analyzed genome-wide maps of RBP association and R-loop formation in the budding yeast S. cerevisiae.

On the one hand, we have investigated whether specific mRNP biogenesis pathways could take place for mRNAs encoding the subunits of multiprotein complexes. Focusing on the Nuclear Pore, we highlighted a trans-acting mechanism that collectively target the mRNAs encoding the components of this complex, and prevent the accumulation of unassembled subunits. On the other hand, we have searched for cis-acting genomic features regulating R-loop formation. Surprisingly, we found that the presence of introns mitigates the accumulation of genotoxic R-loops through the recruitment of the spliceosome. Our work thereby reveals how certain structural features of the transcriptome are optimized to guarantee genome and proteome homeostasis.