EVENT : C3BI Seminars – Methodological

Quality control of the transcription by Nonsense-Mediated-mRNA Decay (NMD) revealed by TSS-RNAseq analysis

Speaker : Christophe Malabat,  Research Engineer from Genetics of Macromolecular Interactions Team       Time : 02:00 pm      Starting Date : 07/01/2016     

Location : Retrovirus room – LWOFF (22) ,Institut Pasteur, Paris

Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harbouring premature stop-codons or short upstream open reading frame (uORFs). Our transcription start sites (TSSs) analysis of Saccharomyces cerevisiae cells deficient for RNA degradation pathways revealed that about half of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spurious transcripts that escaped degradation in the nucleus. Moreover, we found that the low specificity of RNA polymerase II TSSs selection generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or starting downstream of the ATG START codon. Despite the low abundance of this last category of isoforms, their presence seems to constrain genomic sequences, as suggested by the significant bias against in-frame ATGs specifically found at the beginning of the corresponding genes and reflected by a depletion of methionines in the N-terminus of the encoded proteins.

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