Species-dependent splice recognition of a cryptic exon resulting from a recurrent intronic CEP290 mutation that causes congenital blindness

International Journal of Molecular Sciences
Alejandro GarantoRob Wj Collin

Abstract

A mutation in intron 26 of CEP290 (c.2991+1655A>G) is the most common genetic cause of Leber congenital amaurosis (LCA), a severe type of inherited retinal degeneration. This mutation creates a cryptic splice donor site, resulting in the insertion of an aberrant exon (exon X) into ~50% of all CEP290 transcripts. A humanized mouse model with this mutation did not recapitulate the aberrant CEP290 splicing observed in LCA patients, suggesting differential recognition of cryptic splice sites between species. To further assess this phenomenon, we generated two CEP290 minigene constructs, with and without the intronic mutation, and transfected these in cell lines of various species. RT-PCR analysis revealed that exon X is well recognized by the splicing machinery in human and non-human primate cell lines. Intriguingly, this recognition decreases in cell lines derived from species such as dog and rodents, and it is completely absent in Drosophila. In addition, other cryptic splicing events corresponding to sequences in intron 26 of CEP290 were observed to varying degrees in the different cell lines. Together, these results highlight the complexity of splice site recognition among different species, and show that care is warranted when...Continue Reading

References

Jul 12, 2002·Nature·Tom Maniatis, Bosiljka Tasic
Aug 14, 2003·Human Molecular Genetics·Yongping YangShyam K Sharan
Sep 10, 2003·Biochemical Pharmacology·Xiao-Li Tian, Martin Paul
Jun 18, 2005·Bioinformatics·G RätschB Schölkopf
Jan 20, 2006·The Journal of Biological Chemistry·Jim VadolasPanayiotis A Ioannou
Jun 10, 2006·Briefings in Bioinformatics·Liliana Florea
Aug 16, 2006·American Journal of Human Genetics·Anneke I den HollanderFrans P M Cremers
Apr 4, 2007·Human Mutation·John NeidhardtWolfgang Berger
Jul 24, 2007·Genomics·Matthew M HimsSusan A Slaugenhaupt
Aug 21, 2007·Human Mutation·Valeska FrankCarsten Bergmann
Jul 18, 2008·Progress in Retinal and Eye Research·Anneke I den HollanderFrans P M Cremers
Aug 7, 2010·Human Mutation·Frauke CoppietersElfride De Baere
Apr 22, 2011·Investigative Ophthalmology & Visual Science·Alejandro GarantoRoser Gonzàlez-Duarte
Jan 26, 2013·Genes & Development·Xavier RocaIan C Eperon
Mar 22, 2013·Human Molecular Genetics·Ron BochnerGil Ast
May 8, 2013·Clinical Genetics·M M Liu, D J Zack

❮ Previous
Next ❯

Citations

Jun 4, 2016·Cell Stem Cell·Thu T DuongJean Bennett
Mar 16, 2017·EMBO Molecular Medicine·Caroline GodfreyVirginia Arechavala-Gomeza
Jul 16, 2020·Animals : an Open Access Journal From MDPI·Merel Ritskes-HoitingaFranck L B Meijboom
Oct 9, 2019·Disease Models & Mechanisms·Annemieke Aartsma-Rus, Maaike van Putten
Nov 27, 2019·Journal of Clinical Medicine·Petros PatsaliMarina Kleanthous
Apr 7, 2021·EMBO Molecular Medicine·Suzan M HammondVirginia Arechavala-Gomeza

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
biopsy

Software Mentioned

Image J

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.