Location: Children's Nutrition Research CenterTitle: Emerging roles of alternative cleavage and polyadenylation (APA) in human disease
|DHARMALINGAM, PRAKASH - Saveetha Institute Of Medical And Technical Sciences|
|MAHALINGAM, RAJASEKARAN - Md Anderson Cancer Center|
|YALAMANCHILI, HARI - Children'S Nutrition Research Center (CNRC)|
|WENG, TINGTING - University Of Texas Health Science Center|
|KARMOUTY-QUINTANA, HARRY - University Of Texas Health Science Center|
|GUHA, ASHRITH - Houston Methodist Research Institute|
|THANDAVARAYAN, RAJARAJAN - Houston Methodist Research Institute|
Submitted to: Journal of Cellular Physiology
Publication Type: Review Article
Publication Acceptance Date: 6/20/2021
Publication Date: 8/11/2021
Citation: Dharmalingam, P., Mahalingam, R., Yalamanchili, H.K., Weng, T., Karmouty-Quintana, H., Guha, A., Thandavarayan, R.A. 2021. Emerging roles of alternative cleavage and polyadenylation (APA) in human disease. Journal of Cellular Physiology. 237:149-160. https://doi.org/10.1002/jcp.30549.
Technical 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.