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Cellular and Molecular Life Sciences

, Volume 74, Issue 9, pp 1721–1739 | Cite as

Dynamic landscape of alternative polyadenylation during retinal development

  • Wenyan Hu
  • Shengguo Li
  • Ji Yeon Park
  • Sridhar Boppana
  • Ting Ni
  • Miaoxin Li
  • Jun Zhu
  • Bin Tian
  • Zhi Xie
  • Mengqing Xiang
Original Article

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.

Keywords

Central nervous system PA-seq RNA stability Post-transcriptional gene regulation Transcriptome Cleavage and polyadenylation-associated factor 

Notes

Acknowledgements

We thank Dr. Kangxin Jin for critical reading of and thoughtful comments on the manuscript. This work was supported by the China Postdoctoral Science Foundation (2015M582461) to HWY; the National Basic Research Program (973 Program) of China (2015CB964600), the National Institutes of Health (EY020849 and EY012020), and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology, Sun Yat-sen University to MX; and the National Natural Science Foundation of China (31471232), Major Program of Science and Technology of Guangzhou (201607020001), Science and Technology Planning Projects of Guangdong Province (2014B030301040), and Joint Research Fund for Overseas Natural Science of China (3030901001222) to ZX.

Supplementary material

18_2016_2429_MOESM1_ESM.pdf (1.9 mb)
Supplementary material 1 (PDF 1929 kb)

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Wenyan Hu
    • 1
  • Shengguo Li
    • 2
  • Ji Yeon Park
    • 3
  • Sridhar Boppana
    • 2
  • Ting Ni
    • 4
  • Miaoxin Li
    • 5
  • Jun Zhu
    • 6
  • Bin Tian
    • 3
  • Zhi Xie
    • 1
  • Mengqing Xiang
    • 1
    • 2
  1. 1.State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhouChina
  2. 2.Center for Advanced Biotechnology and Medicine and Department of PediatricsRutgers University-Robert Wood Johnson Medical SchoolPiscatawayUSA
  3. 3.Department of Microbiology, Biochemistry and Molecular GeneticsRutgers New Jersey Medical SchoolNewarkUSA
  4. 4.State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life SciencesFudan UniversityShanghaiChina
  5. 5.Department of Medical Genetics, Center for Genome Research, Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina
  6. 6.Systems Biology Center, National Heart, Lung and Blood InstituteNational Institutes of HealthBethesdaUSA

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