Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.

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.

• Authors: Charlotte Capitanchik, Charles R Dixon, Selene K Swanson, Laurence Florens, Alastair R W Kerr, Eric C Schirmer
• Journal: Nucleus (Austin, Tex.) (Nucleus) Vol. 9 Issue 1 Pg. 410-430 ( 2018) ISSN: 1949-1042 [Electronic] United States
• PMID: 29912636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nuclear Proteins
• RNA, Messenger

Topics

• Alternative Splicing (genetics)
• Animals
• Cells, Cultured
• Databases, Nucleic Acid
• Datasets as Topic
• Mice
• Muscle, Skeletal (metabolism)
• Nuclear Envelope (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Organ Specificity (genetics)
• RNA, Messenger (analysis, genetics)