%0 Journal Article %A Capitanchik, Charlotte %A Dixon, Charles R. %A Swanson, Selene K. %A Florens, Laurence %A Kerr, Alastair R. W. %A Schirmer, Eric C. %D 2019 %T Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins %U https://tandf.figshare.com/articles/journal_contribution/Analysis_of_RNA-Seq_datasets_reveals_enrichment_of_tissue-specific_splice_variants_for_nuclear_envelope_proteins/6886352 %R 10.6084/m9.figshare.6886352.v3 %2 https://tandf.figshare.com/ndownloader/files/13198697 %K Tissue-specific %K nuclear membrane %K proteomics %K muscular dystrophy %K nuclear envelopathies %K splice variant %X

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.

%I Taylor & Francis