We focus on RNA quality control mechanisms and their consequences for the cells. Our previous studies revealed, for example, unexpected properties of the transcription process, such as its high pervasiveness and the intrinsic bi-directionality of RNA polymerase II promoters. Our most recent work identified hundreds of alternative start sites for transcription in yeast and highlighted the role of cytoplasmic, non-sense mediated mRNA decay (NMD), and nuclear, exosome, degradation processes in shaping the eukaryotic transcriptome (Malabat, Fernbach et al., eLife 2015) .
Cryptic Unstable Transcripts (CUT) were described by us and our collaborators as a novel class of ubiquitous transcripts that are normally very efficiently degraded by the combined action of a poly-adenylation complex (TRAMP) and of the nuclear exosome (La Cava et al., Cell 2005; Wyers et al., Cell 2005). CUTs are very abundant in mutant strains that lack the degradation or poly-adenylation activities. The study of CUTs gave hints to understand cellular processes as diverse as transcription initiation and termination (Gudipati et al., EMBO J 2012), nucleo-cytoplasmic transport and translation. We have exhaustively mapped the position and abundance of yeast CUTs (Neil et al., Nature 2009). The association of CUTs with gene promoters strongly suggested that eucaryotic promoters are intrinsically bidirectional (for a review, see Jacquier A, Nat Rev Genet 2009).
While nuclear degradation of undesirable RNA can be highly efficient on some transcripts, others are exported to the cytoplasm and are only recognized as unfit for protein synthesis by active translation. Thus, what is usually called ‘transcriptome’ is a reflection of RNA polymerase II activity in balance with various degradation processes. Comprehension of both transcription and of the factors that ensure the stability of mRNA are a key to understand gene expression and its regulation. We developed sequencing-based methods that map transcription ends at nucleotide resolution for RNA and we are currently investigating how environmental changes or individual proteins affect both transcription and genome-wide stability of RNA.
Resource: Browse our genome-wide yeast CUTs abundance and localization results (Neil et al., Nature 2009)