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Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders

by Jamie Nourse 1,2, Stefano Spada 1,2 and Sven Danckwardt 1,2,3,*
1
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
2
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
3
German Center for Cardiovascular Research (DZHK), Rhine-Main, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 915; https://doi.org/10.3390/biom10060915
Received: 27 May 2020 / Revised: 10 June 2020 / Accepted: 13 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Ribonucleoprotein Particles (RNPs): From Structure to Function)
A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of diverse physiological processes. It is therefore not surprising that disruptions of CPA and APA can lead to devastating disorders. Here, we review potential CPA and APA mechanisms involving both loss and gain of function that can have tremendous impacts on health and disease. Ultimately we highlight the emerging diagnostic and therapeutic potential CPA and APA offer. View Full-Text
Keywords: 3′ end processing; cleavage and polyadenylation; alternative polyadenylation; cardiovascular disorders; neurodegenerative disorders; cancer; disease; biomarker; therapy 3′ end processing; cleavage and polyadenylation; alternative polyadenylation; cardiovascular disorders; neurodegenerative disorders; cancer; disease; biomarker; therapy
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Nourse, J.; Spada, S.; Danckwardt, S. Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders. Biomolecules 2020, 10, 915.

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