The role of SMG6 and PM/Sc 100 ribonucleases in messenger RNA degradation mechanisms

• Autor(a) principal: Guedes, Ana Raquel Dias Pereira
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/17151
• topic: Biologia molecular e celular; Ácido ribonucleico; Ribonuclease; Transcrição genética

Eukaryotic gene expression comprises a series of interconnected steps, from transcription to protein synthesis, in which messenger RNAs (mRNAs) are the key intermediates. While the multitude of events that take place throughout the whole process allows for the production of proteins to be controlled at many levels, ensuring maximum efficiency and fidelity, it also makes gene expression susceptible to errors. Eukaryotic cells have developed intricate mRNA quality control mechanisms that recognize and degrade aberrant transcripts. Two examples of these mechanisms are the nonsense-mediated mRNA decay (NMD), which targets mRNAs with premature translation termination codons (PTCs), and the nonstop mRNA decay (NSD), which eliminates mRNAs lacking any in-frame translation termination codons. SMG6 and PM/Scl100 are both ribonucleases which have been implicated in mRNA degradation pathways. One of the mechanisms proposed for mammalian NMD involves an endonucleolytic cleavage of transcripts in the vicinity of the PTC catalyzed by SMG6. On the other hand, the human exosome, which includes the catalytic subunit PM/Scl100, has been associated not only with mRNA surveillance mechanisms, but also with normal mRNA turnover. However, questions relative to the specificity or indispensability of these enzymes in the pathways in which they participate have not yet been answered. The present work aimed to explore the role of SMG6 and PM/Scl100 ribonucleases in the degradation of normal or NSD- and NMD-sensitive mRNAs. The results obtained point to the involvement of SMG6, not only in NMD, but also in NSD and normal mRNA turnover. Moreover, they suggest that SMG6 plays an indirect role on the degradation of NMD targets. PM/Scl100 also appears to intervene in NMD, NSD and normal mRNA turnover; however, the results herein presented suggest that the main contribution to NMD-eliciting transcripts 3’→5’ degradation may be offered by other exoribonucleases.