Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins. (31st December 2018)

• Record Type: Journal Article
• Authors: Capitanchik, Charlotte; Dixon, Charles R.; Swanson, Selene K.; Florens, Laurence; Kerr, Alastair R. W.; Schirmer, Eric C.
• Is Part Of: Nucleus. Volume 9:Number 1(2018)
• Page Start: 410
• Page End: 430
• Publication Date: 2018-12-31
• Subjects: Tissue-specific -- nuclear membrane -- proteomics -- muscular dystrophy -- nuclear envelopathies -- splice variant; Cell nuclei -- Periodicals; Biology -- Periodicals; Biology; Cell nuclei; Periodicals; 571.6605
• DOI: 10.1080/19491034.2018.1469351
• Languages: English
• ISSNs: 1949-1034

Abstract

ABSTRACT: Laminopathies yield tissue-specific pathologies, yet arise from mutation of ubiquitously-expressed genes. A little investigated hypothesis to explain this is that the mutated proteins or their partners have tissue-specific splice variants. To test this, we analyzed RNA-Seq datasets, finding novel isoforms or isoform tissue-specificity for: Lap2, linked to cardiomyopathy; Nesprin 2, linked to Emery-Dreifuss muscular dystrophy and Lmo7, that regulates the Emery-Dreifuss muscular dystrophy linked emerin gene. Interestingly, the muscle-specific Lmo7 exon is rich in serine phosphorylation motifs, suggesting regulatory function. Muscle-specific splice variants in non-nuclear envelope proteins linked to other muscular dystrophies were also found. Nucleoporins tissue-specific variants were found for Nup54, Nup133, Nup153 and Nup358/RanBP2. RT-PCR confirmed novel Lmo7 and RanBP2 variants and specific knockdown of the Lmo7 variantreduced myogenic index. Nuclear envelope proteins were enriched for tissue-specific splice variants compared to the rest of the genome, suggesting that splice variants contribute to its tissue-specific functions.