In eukaryotes, hundreds of proteins and small non-coding RNAs parti­cipate in post-transcriptional processes and their regulation. Many act on bulk mRNA, others regulate specific transcripts. A subset of these factors, with functions in translational repression, miRNA-mediated silencing, mRNA quality control and degradation, co-localize in discrete cytoplasmic foci referred to as mRNA processing bodies or P-bodies, suggesting that post-transcriptional processes are interlinked. For this reason, we are investigating post-transcriptional processes not in isolation, but as a complex network of regulatory circuits that together determine the expression levels of many genes. Our contributions to the current understanding of these processes are summarized below.

In eukaryotes, messenger RNAs harboring nonsense codons (or PTCs) are degraded by a conserved quality-control mechanism known as non­sense-mediated mRNA decay (NMD), which prevents the accumulation of truncated and potentially harmful proteins. We were the first to show that in metazoans, degradation of PTC-containing mRNAs is initiated by an endonucleolytic cleavage occurring in the vicinity of the PTC.

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