Emerging roles of alternative cleavage and polyadenylation (APA) in human disease

Prakash Dharmalingam, Rajasekaran Mahalingam, Hari Krishna Yalamanchili, Tingting Weng, Harry Karmouty-Quintana, Ashrith Guha, Rajarajan A. Thandavarayan

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - 2021

Keywords

  • 3'-UTR
  • RNA binding proteins
  • RNA biology
  • alternative cleavage and polyadenylation
  • mRNA maturation
  • polyadenylation

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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