The conserved alternative splicing factor caper regulates neuromuscular phenotypes during development and aging.
The conserved alternative splicing factor caper regulates neuromuscular phenotypes during development and aging.
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DOI：
10.1016/j.ydbio.2021.01.011
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发表时间：
2021-05
影响因子：
2.7
通讯作者：
Olesnicky EC
中科院分区：
文献类型：
--
作者：
Titus MB;Wright EG;Bono JM;Poliakon AK;Goldstein BR;Super MK;Young LA;Manaj M;Litchford M;Reist NE;Killian DJ;Olesnicky EC
RNA结合蛋白在整个神经系统转录后基因表达的调节中发挥着重要作用。在许多神经退行性疾病和神经发育障碍中，编码 RNA 剪接因子和其他 RNA 结合蛋白的基因普遍存在突变，凸显了这一点。高度保守的选择性剪接因子 Caper 在整个发育胚胎中广泛表达，并在果蝇周围神经系统中各种感觉神经亚型的发育中发挥作用。在这里，我们发现刺山柑功能障碍导致异常的神经肌肉接头形态发生，以及幼虫和成虫阶段的异常运动行为。尽管其广泛表达，我们的结果表明，与肌肉相反，刺山柑功能在神经系统内更大程度地需要用于神经肌肉接头的发育和成人运动行为的调节。此外，我们发现 Caper 与 RNA 结合蛋白 Fmrp 相互作用来调节成年运动行为。最后，我们发现刺山柑功能障碍会导致各种具有性别和年龄偏差的表型，这两者在人类神经退行性疾病中都很常见。
RNA-binding proteins play an important role in the regulation of post-transcriptional gene expression throughout the nervous system. This is underscored by the prevalence of mutations in genes encoding RNA splicing factors and other RNA-binding proteins in a number of neurodegenerative and neurodevelopmental disorders. The highly conserved alternative splicing factor Caper is widely expressed throughout the developing embryo and functions in the development of various sensory neural subtypes in the Drosophila peripheral nervous system. Here we find that caper dysfunction leads to aberrant neuromuscular junction morphogenesis, as well as aberrant locomotor behavior during larval and adult stages. Despite its widespread expression, our results indicate that caper function is required to a greater extent within the nervous system, as opposed to muscle, for neuromuscular junction development and for the regulation of adult locomotor behavior. Moreover, we find that Caper interacts with the RNA-binding protein Fmrp to regulate adult locomotor behavior. Finally, we show that caper dysfunction leads to various phenotypes that have both a sex and age bias, both of which are commonly seen in neurodegenerative disorders in humans.
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DOI：
10.1006/bbrc.2002.6768
发表时间：
2002-04-12
影响因子：
3.1
作者：
Denman, RB;Sung, YJ
通讯作者：
Sung, YJ
影响因子：
16.2
作者：
Barbee, Scott A.;Estes, Patricia S.;Ramaswami, Mani
通讯作者：
Ramaswami, Mani
影响因子：
1.9
作者：
Feng, YF;Ueda, A;Wu, CF
通讯作者：
Wu, CF
影响因子：
3.5
作者：
Coyne, Alyssa N.;Yamada, Shizuka B.;Zarnescu, Daniela C.
通讯作者：
Zarnescu, Daniela C.
影响因子：
7.1
作者：
Huang, Shih-Ling;Wu, Lien-Szu;Shen, Che-Kun James
通讯作者：
Shen, Che-Kun James