Assessing the Prevalence of Transcription Readthrough in healthy tissues through computational approaches

• Autor(a) principal: Luz, Mariana de Almeida Caetano Perdigão
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/151109
• topic: Readthrough transcription; transcription termination; non-coding RNAs; transcriptomics; bioinformatics; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Transcription termination is a crucial step in the creation of functional RNAs and proteins. In fact, inefficient termination has been shown to lead to the production of aberrantly long transcripts through a phenomenon called transcription readthrough (TRT), in renal cancer cells and cells undergoing several different types of stress (such as hyperosmotic, oxidative and heat shock). Despite the growing research interest in this topic, the prevalence of this phenomenon had yet to be studied in healthy tissues. Therefore, my goal was to assess the prevalence of TRT events in healthy human tissues and characterise them. Using computational approaches to analyse human transcriptome profiles revealed that approximately 19% of expressed genes in healthy human tissues produce readthrough (RT) transcripts. In roughly 2% of these TRT events, the RT transcript was found to not only include the intergenic region but to also overlap downstream genes. This analysis also revealed that, on average, genes that produced RT transcripts (RT genes) were more highly expressed than those that did not (NRT genes). Furthermore, RT genes were found to be significantly enriched for protein-coding genes and a significant overlap between RT genes across all tissues was observed, suggesting that TRT is not a stochastic phenomenon but instead determined by still unknown gene features. This work shows unequivocally that TRT is not only prevalent in cells undergoing stress or in disease but also in healthy human tissues.