Alternative polyadenylation: methods, mechanism, function, and role in cancer

Journal of Experimental & Clinical Cancer Research

Qiongzi Qiu¹  Qing Zhou¹  Yan Lu²  Jinwang Ding³  Yi Zhang⁴  Lian Liu⁴  Pengyuan Liu⁵ 

[1] Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China;Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China;Cancer Center, Zhejiang University, 310029, Hangzhou, Zhejiang, China;Department of Head and Neck Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, 310022, Hangzhou, Zhejiang, China;Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310016, Hangzhou, Zhejiang, China;Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310016, Hangzhou, Zhejiang, China;Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, 53226, Milwaukee, WI, USA;Cancer Center, Zhejiang University, 310029, Hangzhou, Zhejiang, China;

关键词: Alternative polyadenylation (APA);    3’UTR;    Poly(A) sites usage;    Cancer;   

DOI  :  10.1186/s13046-021-01852-7

来源: Springer

【 摘 要 】

Occurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3’ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene. As a key molecular mechanism, APA is involved in various gene regulation steps including mRNA maturation, mRNA stability, cellular RNA decay, and protein diversification. APA is frequently dysregulated in cancers leading to changes in oncogenes and tumor suppressor gene expressions. Recent studies have revealed various APA regulatory mechanisms that promote the development and progression of a number of human diseases, including cancer. Here, we provide an overview of four types of APA and their impacts on gene regulation. We focus particularly on the interaction of APA with microRNAs, RNA binding proteins and other related factors, the core pre-mRNA 3’end processing complex, and 3’UTR length change. We also describe next-generation sequencing methods and computational tools for use in poly(A) signal detection and APA repositories and databases. Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.

【 授权许可】

CC BY