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Integrative RNA-seq and ATAC-seq analyses of phosphodiesterase 6 mutation-induced retinitis pigmentosa

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Abstract

Purpose

Inhibition of poly-ADP-ribose polymerase 1 (PARP1) could relieve phosphodiesterase 6 mutation-induced retinitis pigmentosa (RP). However, the mechanism related to PARP1 overexpression in the RP has not been clarified. We attempted to explore the potential mechanism related to PARP1 regulating RP.

Methods

ATAC-seq and RNA-seq were performed for retina tissues of C3H and rd1 mice. The differentially expressed genes (DEGs) were identified, followed by the construction of PARP1-DEG co-expression and protein–protein interaction (PPI) networks. Gene ontology-biological process and pathway enrichment of DEGs were performed by clusterProfiler software. The overlapped genes that might play regulatory roles in PARP1 expression were mined by integrated analysis of RNA-seq and ATAC-seq data.

Results

A total of 1061 DEGs were identified between C3H and rd1 group. Co-expression network was constructed with 313 PARP1-gene co-expression pairs. The down-regulated DEGs were closely related to visual perception and light stimulus-related biological process, while the up-regulated DEGs were significantly enriched in phototransduction and PPAR signaling pathway. PPI network was constructed with 202 nodes and 375 edges, which was clustered into 3 modules. Module 1 genes were closely related to detection of light stimulus, visual perception related biological process and phototransduction pathway (involved with Gnat1/Guca1b/Gnat2/Sag/Pde6g). By integrated analysis of the RNA-seq and ATAC-seq, the overlapped up-regulated genes were Asxl3 and Nyap2, while the down-regulated genes were Tmem136 and Susd3.

Conclusion

Gnat1 may play a key role in RP development by interacting with PARP1. Susd3 may play a regulatory role in PARP1 expression and affect RP formation.

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References

  1. Campochiaro PA, Mir TA (2018) The mechanism of cone cell death in retinitis pigmentosa. Prog Retin Eye Res 62:24–37

    Article  CAS  Google Scholar 

  2. Zhang Q (2016) Retinitis pigmentosa: progress and perspective. Asia Pac J Ophthalmol (Phila) 5(4):265–271

    Article  CAS  Google Scholar 

  3. Parmeggiani F (2011) Clinics, epidemiology and genetics of retinitis pigmentosa. Curr Genom 12(4):236–237

    Article  CAS  Google Scholar 

  4. Schon C et al (2017) Gene therapy successfully delays degeneration in a mouse model of PDE6A-linked retinitis pigmentosa (RP 43). Hum Gene Ther 28:1180–1182

    Article  Google Scholar 

  5. Kim JY et al (2017) Epiretinal membrane formation after intravitreal autologous stem cell implantation in a retinitis pigmentosa patient. Retin Cases Brief Rep 11(3):227–231

    Article  Google Scholar 

  6. Kaur J et al (2011) Calpain and PARP activation during photoreceptor cell death in P23H and S334ter rhodopsin mutant rats. PLoS One 6(7):e22181

    Article  CAS  Google Scholar 

  7. Gopalakrishna KN, Boyd K, Artemyev NO (2017) Mechanisms of mutant PDE6 proteins underlying retinal diseases. Cell Signal 37:74–80

    Article  CAS  Google Scholar 

  8. Dvir L et al (2010) Autosomal-recessive early-onset retinitis pigmentosa caused by a mutation in PDE6G, the gene encoding the gamma subunit of rod cGMP phosphodiesterase. Am J Hum Genet 87(2):258–264

    Article  CAS  Google Scholar 

  9. Andrabi SA et al (2006) Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci U S A 103(48):18308–18313

    Article  CAS  Google Scholar 

  10. Hottiger MO (2011) ADP-ribosylation of histones by ARTD1: an additional module of the histone code? FEBS Lett 585(11):1595–1599

    Article  CAS  Google Scholar 

  11. Thomas C, Tulin AV (2013) Poly-ADP-ribose polymerase: machinery for nuclear processes. Mol Aspects Med 34(6):1124–1137

    Article  CAS  Google Scholar 

  12. Jiao K et al (2016) Efficacy of PARP inhibition in Pde6a mutant mouse models for retinitis pigmentosa depends on the quality and composition of individual human mutations. Cell Death Discov 2:16040

    Article  CAS  Google Scholar 

  13. Sothilingam V et al (2015) Retinitis pigmentosa: impact of different Pde6a point mutations on the disease phenotype. Hum Mol Genet 24(19):5486–5499

    Article  CAS  Google Scholar 

  14. Keeler CE (1924) The inheritance of a retinal abnormality in white mice. Proc Natl Acad Sci U S A 10(7):329–333

    Article  CAS  Google Scholar 

  15. Szklarczyk D et al (2014) STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43:D447–D452

    Article  Google Scholar 

  16. Tang Y et al (2015) CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. BioSystems 127:67–72

    Article  CAS  Google Scholar 

  17. Bandettini WP et al (2012) MultiContrast delayed enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study. J Cardiovasc Magn Reson 14:83

    Article  Google Scholar 

  18. Ashburner M et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25(1):25–29

    Article  CAS  Google Scholar 

  19. Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30

    Article  CAS  Google Scholar 

  20. Yu G et al (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16(5):284–287

    Article  CAS  Google Scholar 

  21. Sahaboglu A et al (2020) Drug repurposing studies of PARP inhibitors as a new therapy for inherited retinal degeneration. Cell Mol Life Sci 77(11):2199–2216

    Article  CAS  Google Scholar 

  22. Kim MS, Joo K (2019) Genetic mutation profiles in korean patients with inherited retinal diseases. J Korean Med Sci 34(21):e161

  23. Yeo JH et al (2019) Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases. Invest Ophthalmol Vis Sci 60(5):1519–1526

    Article  CAS  Google Scholar 

  24. Prem Senthil M, Khadka J, Pesudovs K (2017) Seeing through their eyes: lived experiences of people with retinitis pigmentosa. Eye (Lond) 31(5):741–748

    Article  CAS  Google Scholar 

  25. Mendes HF et al (2005) Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med 11(4):177–185

    Article  CAS  Google Scholar 

  26. Yanagi Y (2008) Role of peoxisome proliferator activator receptor gamma on blood retinal barrier breakdown. PPAR Res 2008:1–4

    Article  Google Scholar 

  27. Donato L et al (2020) Transcriptome analyses of lncRNAs in A2E-stressed retinal epithelial cells unveil advanced links between metabolic impairments related to oxidative stress and retinitis pigmentosa. Antioxidants (Basel) 9(4):318

    Article  CAS  Google Scholar 

  28. Holman RT et al (1994) Abnormal plasma lipids of patients with retinitis pigmentosa. Lipids 29(1):61–65

    Article  CAS  Google Scholar 

  29. Szabo V et al (2007) p.Gln200Glu, a putative constitutively active mutant of rod alpha-transducin (GNAT1) in autosomal dominant congenital stationary night blindness. Hum Mutat 28(7):741–2

    Article  Google Scholar 

  30. Carrigan M, Duignan E (2016) A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration. Br J Ophthalmol 100(4):495–500

    Article  Google Scholar 

  31. Yu Z et al (2015) Sushi domain-containing protein 3: a potential target for breast cancer. Cell Biochem Biophys 72(2):321–324

    Article  CAS  Google Scholar 

  32. Postel K et al (2013) Analysis of cell surface markers specific for transplantable rod photoreceptors. Mol Vis 19:2058–2067

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by grants from the Yunnan Applied Basic Research Projects (No. 2019FB093).

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Author notes

  1. Wenrong Xu and Yan Li have equal first authors.

Authors and Affiliations

  1. Kunming Medical University, Kunming, 650500, Yunnan, China

    Wenrong Xu, Yujie Dong, Libo Xiao, Lan Li & Kangwei Jiao

  2. Department of Ophthalmology, Affiliated Hospital of Yunnan University, Yunnan University, 650021, Kunming, China

    Yan Li, Yujie Dong, Libo Xiao & Kangwei Jiao

  3. Department of Ophthalmology, The Affiliated Calmette Hospital of Kunming Medical University, 650024, Kunming, Yunnan, China

    Wenrong Xu & Lan Li

  4. Key Laboratory of Yunnan Province, Yunnan Eye Institute, Yunnan University, 176 Qingnian, Kunming, 650021, China

    Yan Li, Yujie Dong, Libo Xiao & Kangwei Jiao

Authors
  1. Wenrong Xu
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  2. Yan Li
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  3. Yujie Dong
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  4. Libo Xiao
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  5. Lan Li
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Correspondence to Lan Li or Kangwei Jiao.

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Xu, W., Li, Y., Dong, Y. et al. Integrative RNA-seq and ATAC-seq analyses of phosphodiesterase 6 mutation-induced retinitis pigmentosa. Int Ophthalmol 42, 2385–2395 (2022). https://doi.org/10.1007/s10792-022-02238-0

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  • DOI: https://doi.org/10.1007/s10792-022-02238-0

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