Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.
Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.
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DOI：
10.1080/19491034.2018.1469351
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Schirmer EC
中科院分区：
文献类型：
--
作者：
Capitanchik C;Dixon CR;Swanson SK;Florens L;Kerr ARW;Schirmer EC
核纤层病产生组织特异性病理学，但由普遍表达的基因突变引起。一个小的研究假设来解释这一点是，突变的蛋白质或其合作伙伴有组织特异性剪接变体。为了测试这一点，我们分析了RNA-Seq数据集，发现了新的同种型或同种型组织特异性：Lap 2，与心肌病相关; Nesprin 2，与Emery-Dreifuss肌营养不良症相关; Lmo 7，调节Emery-Dreifuss肌营养不良症相关的emerin基因。有趣的是，肌肉特异性Lmo 7外显子富含丝氨酸磷酸化基序，表明其具有调节功能。在与其他肌营养不良症相关的非核膜蛋白中也发现了肌肉特异性剪接变异体。核孔蛋白组织特异性变异体被发现为Nup 54、Nup 133、Nup 153和Nup 358/RanBP 2。RT-PCR证实了新的Lmo 7和RanBP 2变异体，并且特异性敲低Lmo 7变异体可降低生肌指数。与基因组的其余部分相比，核膜蛋白富含组织特异性剪接变体，这表明剪接变体有助于其组织特异性功能。
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.
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影响因子：
4.9
作者：
Doynova MD;Markworth JF;Cameron-Smith D;Vickers MH;O'Sullivan JM
通讯作者：
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通讯作者：
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