Department of Biochemistry and Molecular Pharmacology
*Alternative Splicing; Animals; Binding Sites; Cell Line, Tumor; Exons; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Inverted Repeat Sequences; Mice; Myelin-Associated Glycoprotein; *Nucleic Acid Conformation; Protein Binding; Protein Interaction Mapping; RNA Isoforms; RNA Splice Sites; RNA, Messenger; Spliceosomes
Biochemistry | Genetics | Molecular Biology | Molecular Genetics | Nervous System
Myelin-associated glycoprotein (MAG) is a major component of myelin in the vertebrate central nervous system. MAG is present in the periaxonal region of the myelin structure, where it interacts with neuronal proteins to inhibit axon outgrowth and protect neurons from degeneration. Two alternatively spliced isoforms of Mag mRNA have been identified. The mRNA encoding the shorter isoform, known as S-MAG, contains a termination codon in exon 12, while the mRNA encoding the longer isoform, known as L-MAG, skips exon 12 and produces a protein with a longer C-terminal region. L-MAG is required in the central nervous system. How inclusion of Mag exon 12 is regulated is not clear. In a previous study, we showed that heteronuclear ribonucleoprotein A1 (hnRNP A1) contributes to Mag exon 12 skipping. Here, we show that hnRNP A1 interacts with an element that overlaps the 5' splice site of Mag exon 12. The element has a reduced ability to interact with the U1 snRNP compared with a mutant that improves the splice site consensus. An evolutionarily conserved secondary structure is present surrounding the element. The structure modulates interaction with both hnRNP A1 and U1. Analysis of splice isoforms produced from a series of reporter constructs demonstrates that the hnRNP A1-binding site and the secondary structure both contribute to exclusion of Mag exon 12.
Mag, alternative splicing, hnRNP A1, myelin, myelin-associated glycoprotein, secondary structure
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Copyright © 2013; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
DOI of Published Version
RNA. 2013 Jul;19(7):948-57. doi: 10.1261/rna.036780.112. Epub 2013 May 23. Link to article on publisher's site
RNA (New York, N.Y.)
Zearfoss, Nancy R.; Johnson, Emily S.; and Ryder, Sean P., "hnRNP A1 and secondary structure coordinate alternative splicing of Mag" (2013). University of Massachusetts Medical School Faculty Publications. 496.
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This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License