title: Dynamic landscape of alternative polyadenylation during retinal development.
abstract: The development of the central nervous system (CNS) is a complex process that must be exquisitely controlled at multiple levels to ensure the production of appropriate types and quantity of neurons. RNA alternative polyadenylation (APA) contributes to transcriptome diversity and gene regulation, and has recently been shown to be widespread in the CNS. However, the previous studies have been primarily focused on the tissue specificity of APA and developmental APA change of whole model organisms; a systematic survey of APA usage is lacking during CNS development. Here, we conducted global analysis of APA during mouse retinal development, and identified stage-specific polyadenylation (pA) sites that are enriched for genes critical for retinal development and visual perception. Moreover, we demonstrated 3'UTR (untranslated region) lengthening and increased usage of intronic pA sites over development that would result in gaining many different RBP (RNA-binding protein) and miRNA target sites. Furthermore, we showed that a considerable number of polyadenylated lncRNAs are co-expressed with protein-coding genes involved in retinal development and functions. Together, our data indicate that APA is highly and dynamically regulated during retinal development and maturation, suggesting that APA may serve as a crucial mechanism of gene regulation underlying the delicate process of CNS development.
authors.affiliation: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 500040, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Hu
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School, 679 Hoes Lane West, Piscataway, NJ, 08854, USA.
authors.forename: Shengguo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, 07101, USA.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School, 679 Hoes Lane West, Piscataway, NJ, 08854, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Boppana
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ni
authors.affiliation: Department of Medical Genetics, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Li
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, 07101, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 500040, China. xiezhi@gmail.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 500040, China. xiangmq3@mail.sysu.edu.cn.|Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School, 679 Hoes Lane West, Piscataway, NJ, 08854, USA. xiangmq3@mail.sysu.edu.cn.
authors.forename: Mengqing
authors.initials: M
authors.lastname: Xiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D018507:Gene Expression Regulation, Developmental; D008810:Mice, Inbred C57BL; D059372:Nucleotide Motifs / Q000235:genetics; D026723:Polyadenylation / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D020413:3' Untranslated Regions; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: Central nervous system; Cleavage and polyadenylation-associated factor; PA-seq; Post-transcriptional gene regulation; RNA stability; Transcriptome