Transcription readthrough is prevalent in healthy human tissues and associated with inherent genomic features

Caldas, Paulo; Luz, Mariana; Baseggio, Simone; Andrade, Rita; Sobral, Daniel; Grosso, Ana Rita

http://hdl.handle.net/10362/166844

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Resumo(s)

Transcription termination is a crucial step in the production of conforming mRNAs and functional proteins. Under cellular stress conditions, the transcription machinery fails to identify the termination site and continues transcribing beyond gene boundaries, a phenomenon designated as transcription readthrough. However, the prevalence and impact of this phenomenon in healthy human tissues remain unexplored. Here, we assessed transcription readthrough in almost 3000 transcriptome profiles representing 23 human tissues and found that 34% of the expressed protein-coding genes produced readthrough transcripts. The production of readthrough transcripts was restricted in genomic regions with high transcriptional activity and was associated with inefficient splicing and increased chromatin accessibility in terminal regions. In addition, we showed that these transcripts contained several binding sites for the same miRNA, unravelling a potential role as miRNA sponges. Overall, this work provides evidence that transcription readthrough is pervasive and non-stochastic, not only in abnormal conditions but also in healthy tissues. This suggests a potential role for such transcripts in modulating normal cellular functions.

Descrição

We thank João Neto, Silvia Carvalho, and the remaining Computational Multi-Omics Lab members at UCIBIO for their helpful comments and suggestions. Paulo Caldas was a recipient of a Marie Skłodowska-Curie Postdoctoral Fellowship (FOX-MTN-HORIZON-MSCA - 2021-PF-01-01). This work was financed by national funds from Fundação para a Ciência e Tecnologia (FCT), in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences (UCIBIO) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Publisher Copyright: © 2024, The Author(s).

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Medicine (miscellaneous) General Biochemistry,Genetics and Molecular Biology General Agricultural and Biological Sciences SDG 3 - Good Health and Well-being