Duncan NRI Faculty and Staff Publications

Language

English

Publication Date

1-1-2022

Journal

Journal of Cellular Physiology

DOI

10.1002/jcp.30549

PMID

34378793

PMCID

PMC12079706

PubMedCentral® Posted Date

5-15-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to APA are largely investigated in human diseases. However, the functions of the core APA machinery and related factors during disease conditions remain largely unknown. In this review, we discuss the roles of polyadenylation machinery in relation to brain disease, cardiac failure, pulmonary fibrosis, cancer, infectious conditions, and other human diseases. Collectively, we believe this review will be a useful avenue for understanding the emerging role of APA in the pathobiology of various human diseases.

Keywords

3' Untranslated Regions, Humans, Polyadenylation, RNA Stability, RNA, Messenger, RNA-Binding Proteins

Published Open-Access

yes

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