TY - JOUR
T1 - Emerging roles of alternative cleavage and polyadenylation (APA) in human disease
AU - Dharmalingam, Prakash
AU - Mahalingam, Rajasekaran
AU - Yalamanchili, Hari Krishna
AU - Weng, Tingting
AU - Karmouty-Quintana, Harry
AU - Guha, Ashrith
AU - A. Thandavarayan, Rajarajan
N1 - Funding Information:
This study was supported by grants from the American Heart Association (19TPA34880039 and 18IPA34170497 R.A.T), 5R01HL138510 to HKQ and the Roswell and Ann Vaughan Fund to A.G. We also thank those who edited the manuscript: Kelli A. Volcik, Department of Biochemistry and Molecular Biology & Divisions of Critical Care, Pulmonary and Sleep Medicine, Department of Internal Medicine, UTHealth–McGovern Medical School, Houston, TX 77030.
Funding Information:
This study was supported by grants from the American Heart Association (19TPA34880039 and 18IPA34170497 R.A.T), 5R01HL138510 to HKQ and the Roswell and Ann Vaughan Fund to A.G. We also thank those who edited the manuscript: Kelli A. Volcik, Department of Biochemistry and Molecular Biology & Divisions of Critical Care, Pulmonary and Sleep Medicine, Department of Internal Medicine, UTHealth?McGovern Medical School, Houston, TX 77030.
Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
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U2 - 10.1002/jcp.30549
DO - 10.1002/jcp.30549
M3 - Review article
C2 - 34378793
AN - SCOPUS:85112063527
SN - 0021-9541
VL - 237
SP - 149
EP - 160
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -