@article{fa27f6f5532e407eb75dce74e836c669,
title = "Defective expression of mitochondrial, vacuolar H+-ATPase and histone genes in a C. Elegans Model of SMA",
abstract = "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.",
keywords = "C. elegans, Histone, Mitochondria, SMN, Vacuolar H-ATPase",
author = "Xiaoyang Gao and Jing Xu and Hao Chen and Dingwu Xue and Wenju Pan and Chuanman Zhou and Ma, {Yongchao C.} and Long Ma",
note = "Funding Information: The study was supported by National Natural Science Foundation of China grants (31371253 and 31571045) and a MOST grant (2016YFC1201805) to LM and by National Institutes of Health grant numbers R01NS094564 and R21NS106307, and grants from The Hartwell Foundation, Cure SMA and the Chicago Biomedical Consortium to YCM. YCM is the Ann Marie and Francis Klocke M.D. Research Scholar supported by the Joseph and Bessie Feinberg Foundation. Funding Information: We thank members of the Ma laboratory for suggestions. Some strains were provided by the CGC, which was funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Publisher Copyright: Copyright {\textcopyright} 2019 Gao, Xu, Chen, Xue, Pan, Zhou, Ma and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
doi = "10.3389/fgene.2019.00410",
language = "English (US)",
volume = "10",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S. A.",
number = "MAY",
}