A retroelement modifies pre-mRNA splicing: The murine Glrbspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion
Becker K, Braune M, Benderska N, Buratti E, Baralle F, Villmann C, Stamm S, Eulenburg V, Becker CM (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Original Authors: Becker K, Braune M, Benderska N, Buratti E, Baralle F, Villmann C, Stamm S, Eulenburg V, Becker CM
Publisher: American Society for Biochemistry and Molecular Biology
Book Volume: 287
Pages Range: 31185-31194
Journal Issue: 37
Abstract
The glycine receptor-deficient mutant mouse spastic carries a full-length long interspersed nuclear element (LINE1) retrotransposon in intron 6 of the glycine receptor β subunit gene, Glrb(spa). The mutation arose in the C57BL/6J strain and is associated with skipping of exon 6 or a combination of the exons 5 and 6, thus resulting in a translational frameshift within the coding regions of the GlyR β subunit. The effect of the Glrb(spa) LINE1 insertion on pre-mRNA splicing was studied using a minigene approach. Sequence comparison as well as motif prediction and mutational analysis revealed that in addition to the LINE1 insertion the inactivation of an exonic splicing enhancer (ESE) within exon 6 is required for skipping of exon 6. Reconstitution of the ESE by substitution of a single residue was sufficient to prevent exon skipping. In addition to the ESE, two regions within the 5' and 3' UTR of the LINE1 were shown to be critical determinants for exon skipping, indicating that LINE1 acts as efficient modifier of subtle endogenous splicing phenotypes. Thus, the spastic allele of the murine glycine receptor β subunit gene is a two-hit mutation, where the hypomorphic alteration in an ESE is amplified by the insertion of a LINE1 element in the adjacent intron. Conversely, the LINE1 effect on splicing may be modulated by individual polymorphisms, depending on the insertional environment within the host genome.
Authors with CRIS profile
Volker Eulenburg
Lehrstuhl für Biochemie und Molekulare Medizin
Cord-Michael Becker
Lehrstuhl für Biochemie und Molekulare Medizin
Involved external institutions
India (IN)How to cite
APA:
Becker, K., Braune, M., Benderska, N., Buratti, E., Baralle, F., Villmann, C.,... Becker, C.-M. (2012). A retroelement modifies pre-mRNA splicing: The murine Glrbspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion. Journal of Biological Chemistry, 287(37), 31185-31194. https://doi.org/10.1074/jbc.M112.375691
MLA:
Becker, Kristina, et al. "A retroelement modifies pre-mRNA splicing: The murine Glrbspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion." Journal of Biological Chemistry 287.37 (2012): 31185-31194.
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