Defective Expression of Mitochondrial, Vacuolar H+-ATPase and Histone Genes in a C. elegans Model of SMA
Defective Expression of Mitochondrial, Vacuolar H+-ATPase and Histone Genes in a C. elegans Model of SMA
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SMA 线虫模型中线粒体、液泡 H-ATP 酶和组蛋白基因的缺陷表达
DOI：
10.3389/fgene.2019.00410
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发表时间：
2019-05
期刊：
影响因子：
--
通讯作者：
Long Ma
中科院分区：
文献类型：
--
作者：
Xiaoyang Gao;Jin Xu;Hao Chen;Dingwu Xue;Wenju Pan;Chuanman Zhou;Yongchao C. Ma;Long Ma
脊髓性肌萎缩症(SMA)是一种由运动神经元存活基因SMN1功能缺失突变引起的严重运动神经元退行性疾病。人们普遍认为，基因表达缺陷是SMA的基础。然而，这些受影响的基因的身份仍有待阐明。通过对秀丽线虫SMA模型症状前期转录组的分析，我们发现许多核编码的线粒体基因和空泡H+-ATPase基因的表达显著下调，而组蛋白基因的表达显著上调。我们先前已经证明，编码关键剪接因子U2AF大亚基的UAF-1基因可以影响SMN-1突变体的行为和寿命。在这里，我们发现SMN-1和UAF-1以基因特异性的方式相互作用，影响3‘和5’剪接位点的识别。总之，我们的结果表明SMN-1和UAF-1在影响RNA剪接方面存在功能相互作用，并可能对线粒体和组蛋白基因的表达产生影响。
Spinal muscular atrophy (SMA) is a severe motor neuron degenerative disease caused by loss-of-function mutations in the survival motor neuron gene SMN1. It is widely posited that defective gene expression underlies SMA. However, the identities of these affected genes remain to be elucidated. By analyzing the transcriptome of a Caenorhabditis elegans SMA model at the pre-symptomatic stage, we found that the expression of numerous nuclear encoded mitochondrial genes and vacuolar H+-ATPase genes was significantly down-regulated, while that of histone genes was significantly up-regulated. We previously showed that the uaf-1 gene, encoding key splicing factor U2AF large subunit, could affect the behavior and lifespan of smn-1 mutants. Here, we found that smn-1 and uaf-1 interact to affect the recognition of 3' and 5' splice sites in a gene-specific manner. Altogether, our results suggest a functional interaction between smn-1 and uaf-1 in affecting RNA splicing and a potential effect of smn-1 on the expression of mitochondrial and histone genes.
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DOI：
10.1016/j.bbagrm.2016.12.008
发表时间：
2017-03
期刊：
Biochimica et biophysica acta. Gene regulatory mechanisms
影响因子：
--
作者：
Singh RN;Howell MD;Ottesen EW;Singh NN
通讯作者：
Singh NN
影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
10.5
作者：
Van Alstyne M;Simon CM;Sardi SP;Shihabuddin LS;Mentis GZ;Pellizzoni L
通讯作者：
Pellizzoni L
影响因子：
3.5
作者：
Gallotta I;Mazzarella N;Donato A;Esposito A;Chaplin JC;Castro S;Zampi G;Battaglia GS;Hilliard MA;Bazzicalupo P;Di Schiavi E
通讯作者：
Di Schiavi E
影响因子：
3.5
作者：
J. Sleigh;S. Buckingham;Behrooz Esmaeili;M. Viswanathan;E. Cuppen;B. Westlund;D. Sattelle
通讯作者：
J. Sleigh;S. Buckingham;Behrooz Esmaeili;M. Viswanathan;E. Cuppen;B. Westlund;D. Sattelle