Epitranscriptome Analysis of Oxidative Stressed Retinal Epithelial Cells Depicted a Possible RNA Editing Landscape of Retinal Degeneration.

A2E IRDs RNA editing RNA-Seq RPE oxidative stress

Journal

Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981

Informations de publication

Date de publication:
30 Sep 2022
Historique:
received: 18 08 2022
revised: 26 09 2022
accepted: 28 09 2022
entrez: 27 10 2022
pubmed: 28 10 2022
medline: 28 10 2022
Statut: epublish

Résumé

Oxidative stress represents one of the principal causes of inherited retinal dystrophies, with many related molecular mechanisms still unknown. We investigated the posttranscriptional RNA editing landscape of human retinal pigment epithelium cells (RPE) exposed to the oxidant agent N-retinylidene-N-retinyl ethanolamine (A2E) for 1 h, 2 h, 3 h and 6 h. Using a transcriptomic approach, refined with a specific multialgorithm pipeline, 62,880 already annotated and de novo RNA editing sites within about 3000 genes were identified among all samples. Approximately 19% of these RNA editing sites were found within 3' UTR, including sites common to all time points that were predicted to change the binding capacity of 359 miRNAs towards 9654 target genes. A2E exposure also determined significant gene expression differences in deaminase family ADAR, APOBEC and ADAT members, involved in canonical and tRNA editing events. On GO and KEGG enrichment analyses, genes that showed different RNA editing levels are mainly involved in pathways strongly linked to a possible neovascularization of retinal tissue, with induced apoptosis mediated by the ECM and surface protein altered signaling. Collectively, this work demonstrated dynamic RNA editome profiles in RPE cells for the first time and shed more light on new mechanisms at the basis of retinal degeneration.

Identifiants

DOI: 10.3390/antiox11101967 PMID: 36290689 PMC: PMC9598096
pubmed: 36290689
pii: antiox11101967
doi: 10.3390/antiox11101967
pmc: PMC9598096
pii:
doi:

Types de publication

Journal Article

Langues

eng

Références

Nucleic Acids Res. 2019 Jan 8;47(D1):D155-D162
pubmed: 30423142
Nucleic Acids Res. 2021 Apr 6;49(6):3354-3370
pubmed: 33660779
Genomics. 2002 Apr;79(4):464-70
pubmed: 11944974
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Science. 2017 Aug 18;357(6352):
pubmed: 28818916
Nature. 2017 Oct 11;550(7675):249-254
pubmed: 29022589
Nucleic Acids Res. 2017 Jan 4;45(D1):D331-D338
pubmed: 27899567
Annu Rev Biochem. 2010;79:321-49
pubmed: 20192758
Nucleic Acids Res. 2014 Jan;42(Database issue):D109-13
pubmed: 24163250
Nucleic Acids Res. 2017 Jan 4;45(D1):D190-D199
pubmed: 27899635
J Cell Sci. 2013 Sep 1;126(Pt 17):3799-804
pubmed: 23970415
Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):1
pubmed: 33523199
Nat Protoc. 2020 Mar;15(3):1098-1131
pubmed: 31996844
PLoS Comput Biol. 2020 Jun 8;16(6):e1007968
pubmed: 32511223
Bioinformatics. 2010 Feb 15;26(4):493-500
pubmed: 20022975
J Physiol Pharmacol. 2009 Oct;60 Suppl 4:31-8
pubmed: 20083849
Methods Mol Biol. 2021;2181:149-162
pubmed: 32729079
Methods Mol Biol. 2021;2181:177-191
pubmed: 32729081
Nat Commun. 2019 Apr 5;10(1):1562
pubmed: 30952866
Transl Vis Sci Technol. 2019 Aug 19;8(4):24
pubmed: 31448181
Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63
pubmed: 24234451
RNA. 2013 Jun;19(6):725-32
pubmed: 23598527
Bioinformatics. 2016 Jan 15;32(2):292-4
pubmed: 26428292
Crit Rev Toxicol. 2021 May;51(5):456-466
pubmed: 34467829
Antioxidants (Basel). 2020 Apr 10;9(4):
pubmed: 32290199
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
Cells. 2021 Jul 06;10(7):
pubmed: 34359873
Antioxidants (Basel). 2021 Jan 29;10(2):
pubmed: 33572785
Trends Mol Med. 2018 Mar;24(3):294-303
pubmed: 29483039
Life (Basel). 2021 Jul 29;11(8):
pubmed: 34440511
Nat Biotechnol. 2012 Feb 12;30(3):253-60
pubmed: 22327324
Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1222-7
pubmed: 11923269
Am J Pathol. 2009 Dec;175(6):2697-708
pubmed: 19893042
FEBS Open Bio. 2018 Jul 31;8(9):1424-1436
pubmed: 30186744
BMB Rep. 2019 Mar;52(3):196-201
pubmed: 30103846
Exp Eye Res. 2021 Aug;209:108641
pubmed: 34058230
Nat Commun. 2019 Nov 20;10(1):5243
pubmed: 31748531
Nutrients. 2021 Jan 25;13(2):
pubmed: 33503991
Int J Mol Sci. 2019 Dec 11;20(24):
pubmed: 31835747
Bioinformatics. 2020 May 1;36(9):2796-2804
pubmed: 32003773
Nucleic Acids Res. 2021 Jan 8;49(D1):D884-D891
pubmed: 33137190
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169
pubmed: 27899622
Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):
pubmed: 34620711
Methods. 2016 Sep 1;107:42-7
pubmed: 27208508
Nucleic Acids Res. 2016 Jan 4;44(D1):D481-7
pubmed: 26656494
Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361
pubmed: 27899662
RNA Biol. 2021 Nov 12;18(sup2):574-585
pubmed: 34672903
Neural Comput Appl. 2021;33(22):15669-15692
pubmed: 34155424
Neurochem Res. 2017 Apr;42(4):1151-1164
pubmed: 28150227
Bioinformatics. 2015 Dec 15;31(24):3906-13
pubmed: 26323713
J Biol Chem. 2012 Jun 22;287(26):22276-86
pubmed: 22570475
Database (Oxford). 2016 Jun 23;2016:
pubmed: 27337980
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Enzymes. 2017;41:299-329
pubmed: 28601225
PLoS One. 2015 Mar 25;10(3):e0120089
pubmed: 25807502
J Mol Biol. 2021 May 28;433(11):166747
pubmed: 33310018
Antioxidants (Basel). 2020 Nov 20;9(11):
pubmed: 33233546
Nat Commun. 2022 Apr 5;13(1):1830
pubmed: 35383196
Trends Genet. 2016 Mar;32(3):165-175
pubmed: 26803450
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Biomol Ther (Seoul). 2022 May 1;30(3):291-297
pubmed: 35074938
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Biochem J. 2022 Feb 17;479(4):561-580
pubmed: 35136964
Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H484-H496
pubmed: 29101181
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Biochimie. 2015 Oct;117:22-7
pubmed: 26051678
Br J Cancer. 2006 Feb 27;94(4):586-92
pubmed: 16404425
Methods Mol Biol. 2021;2181:309-330
pubmed: 32729088
Methods Mol Biol. 2021;2181:51-67
pubmed: 32729074
Aging Cell. 2019 Dec;18(6):e13041
pubmed: 31560156
J Transl Med. 2019 Sep 23;17(1):319
pubmed: 31547885
Food Funct. 2018 Apr 25;9(4):2171-2183
pubmed: 29541735
Cell. 2017 Jun 15;169(7):1187-1200
pubmed: 28622506
Ocul Immunol Inflamm. 2020 Jul 3;28(5):735-738
pubmed: 32589459
FEBS Open Bio. 2018 Jan 02;8(2):219-233
pubmed: 29435412
Cell Mol Life Sci. 2020 Mar;77(5):789-805
pubmed: 31897543
Biomed Khim. 2016 Jul;62(5):510-519
pubmed: 27797325
Nat Rev Mol Cell Biol. 2019 Aug;20(8):457-473
pubmed: 31182865
Methods Mol Biol. 2014;1167:119-27
pubmed: 24823775
Antioxidants (Basel). 2022 May 28;11(6):
pubmed: 35739970
Bioinformatics. 2017 Nov 15;33(22):3538-3548
pubmed: 29036410
Mol Biol (Mosk). 2014 Jan-Feb;48(1):15-21
pubmed: 25842822
Antioxidants (Basel). 2020 Apr 15;9(4):
pubmed: 32326576

Auteurs

Luigi Donato (L)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.
Department of Biomolecular Strategies, Genetics and Cutting-Edge Therapies, I.E.ME.S.T., 90139 Palermo, Italy.
ORCID: 0000-0002-5292-426X

Concetta Scimone (C)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.
Department of Biomolecular Strategies, Genetics and Cutting-Edge Therapies, I.E.ME.S.T., 90139 Palermo, Italy.
ORCID: 0000-0002-4824-1693

Simona Alibrandi (S)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.
Department of Biomolecular Strategies, Genetics and Cutting-Edge Therapies, I.E.ME.S.T., 90139 Palermo, Italy.
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy.

Sergio Zaccaria Scalinci (SZ)

DIMEC (Department of Medical and Surgical Sciences), University of Bologna, 40121 Bologna, Italy.

Carmela Rinaldi (C)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.

Rosalia D'Angelo (R)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.
ORCID: 0000-0001-6510-3121

Antonina Sidoti (A)

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.

Classifications MeSH