Differential stability of variant OPN1LW gene transcripts in myopic patients.

Publisher: Molecular Vision Country of Publication: United States NLM ID: 9605351 Publication Model: eCollection Cited Medium: Internet ISSN: 1090-0535 (Electronic) Linking ISSN: 10900535 NLM ISO Abbreviation: Mol Vis Subsets: MEDLINE

Original Publication: Atlanta Ga : Molecular Vision, 1995-

RNA Splicing* ; RNA Stability*; Myopia/*genetics ; RNA, Messenger/*genetics ; Rod Opsins/*genetics; Adult ; Australia ; Case-Control Studies ; Cloning, Molecular ; Gene Expression ; Genetic Variation ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; HEK293 Cells ; Humans ; Islands ; Male ; Myopia/diagnosis ; Myopia/physiopathology ; Nucleic Acid Conformation ; RNA, Messenger/chemistry ; RNA, Messenger/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Rod Opsins/deficiency ; Sequence Analysis, DNA

Purpose: In Bornholm eye disease, a defect in the splicing of transcripts from a variant OPN1LW opsin gene leads to a depletion in spliced transcript levels and, consequently, a reduction in photopigment in photoreceptors expressing the variant gene.
Methods: Myopic and age-matched control subjects were drawn from the Western Australian Pregnancy Cohort (Raine) Study and the Norfolk Island Eye Study groups. The OPN1LW opsin gene was amplified using long-range PCR methodology and was fully sequenced. Expression of variant opsins was evaluated using quantitative PCR (qPCR). RNA secondary structure changes arising from identified variants were predicted by modeling.
Results: Forty-two nucleotide sites were found to vary across the 111 subjects studied. Of these, 15 had not been previously reported, with three present only in myopic individuals. Expression of these variants in transfected human embryonic kidney (HEK293T) cells demonstrated that splicing efficiencies were not affected. However, gene transcripts from two of the three variants were significantly depleted. RNA secondary structure modeling predicted that these single nucleotide changes could affect RNA stability.
Conclusions: None of the variants identified in myopic individuals appeared to alter the efficiency of transcript splicing. However, two resulted in a significant reduction in the number of spliced and unspliced transcripts, indicating an overall reduction in steady-state transcript stability. Such a change would be expected to result in a reduced amount of photopigment, and this may be a contributing factor in the development of myopia.

Nature. 2015 Mar 19;519(7543):276-8. (PMID: 25788077)
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034. (PMID: 12184808)
J Neurosci. 2005 Jan 19;25(3):748-57. (PMID: 15659613)
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15. (PMID: 12824337)
Invest Ophthalmol Vis Sci. 2011 Jun 01;52(6):3723-9. (PMID: 21357407)
Genome Res. 2015 Nov;25(11):1666-79. (PMID: 26450929)
Biochem Biophys Res Commun. 2012 Jul 20;424(1):152-7. (PMID: 22732407)
J Biol Chem. 1988 Feb 15;263(5):2119-22. (PMID: 3123487)
Biomed Opt Express. 2016 Oct 13;7(11):4554-4568. (PMID: 27895995)
Clin Exp Ophthalmol. 2011 Nov;39(8):734-42. (PMID: 21631679)
Mol Biol Evol. 2001 Aug;18(8):1540-50. (PMID: 11470845)
Hum Mutat. 2008 Jun;29(6):869-78. (PMID: 18412284)
Hum Mol Genet. 2002 Jan 1;11(1):87-92. (PMID: 11773002)
Optom Vis Sci. 2004 May;81(5):317-22. (PMID: 15181356)
Biochem Biophys Res Commun. 2004 Jun 25;319(2):410-8. (PMID: 15178422)
J Neurosci. 2009 Jun 10;29(23):7519-25. (PMID: 19515920)
Mol Cell. 2001 Aug;8(2):375-81. (PMID: 11545739)
Arch Ophthalmol. 2004 Jun;122(6):897-908. (PMID: 15197065)
Curr Opin Ophthalmol. 2009 Sep;20(5):356-62. (PMID: 19587595)
Ophthalmology. 2005 Aug;112(8):1448-54. (PMID: 15953640)
Int J Epidemiol. 2017 Oct 1;46(5):1384-1385j. (PMID: 28064197)
PLoS Genet. 2013;9(2):e1003299. (PMID: 23468642)
Invest Ophthalmol Vis Sci. 2013 Feb 15;54(2):1361-9. (PMID: 23322568)
Genome Res. 1999 Jul;9(7):629-38. (PMID: 10413401)
FASEB J. 2007 Sep;21(11):2713-24. (PMID: 17463225)
Nat Genet. 2013 Mar;45(3):314-8. (PMID: 23396134)
J Mol Biol. 1999 May 21;288(5):911-40. (PMID: 10329189)
Ophthalmic Genet. 2013 Dec;34(4):199-208. (PMID: 23301674)
Biochim Biophys Acta. 2006 Mar;1762(3):304-11. (PMID: 16427773)
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8461-6. (PMID: 15148406)
Hum Mutat. 2014 Nov;35(11):1354-62. (PMID: 25168334)
RNA. 1995 Jul;1(5):453-65. (PMID: 7489507)
Clin Genet. 1990 Oct;38(4):281-6. (PMID: 1980096)
Mol Vis. 2008 Apr 18;14:683-90. (PMID: 18431455)
Eye (Lond). 2014 Feb;28(2):169-79. (PMID: 24406411)
Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1834-1842. (PMID: 28358949)
Mol Genet Genomic Med. 2015 Jul;3(4):327-45. (PMID: 26247049)
Arch Ophthalmol. 2004 Apr;122(4):495-505. (PMID: 15078666)
Hum Mol Genet. 2002 Dec 1;11(25):3209-19. (PMID: 12444105)
Genome Res. 2009 Mar;19(3):415-26. (PMID: 19196633)
J Cell Sci. 2002 Aug 1;115(Pt 15):3033-8. (PMID: 12118059)
Arch Ophthalmol. 1999 May;117(5):658-63. (PMID: 10326965)
Invest Ophthalmol Vis Sci. 2016 Jul 1;57(8):3853-63. (PMID: 27447086)
Cell Mol Life Sci. 2011 Dec;68(24):4115-32. (PMID: 21833582)
J Biol Chem. 2004 Apr 16;279(16):15877-87. (PMID: 14754881)
Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4150-5. (PMID: 26114493)
Singapore Med J. 2004 Oct;45(10):470-4. (PMID: 15455167)
Transl Vis Sci Technol. 2017 May 10;6(3):2. (PMID: 28516000)
Vision Res. 2010 Nov 23;50(23):2396-402. (PMID: 20854834)
Biotechniques. 2007 Dec;43(6):785-9. (PMID: 18251255)

0 (RNA, Messenger)
0 (Recombinant Proteins)
0 (Rod Opsins)
0 (long-wavelength opsin)

Date Created: 20190419 Date Completed: 20190829 Latest Revision: 20200309

20221213

PMC6441357

30996587