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Hypothermia induces changes in the alternative splicing pattern of cold-inducible RNA-binding protein transcripts in a non-hibernator, the mouse.
Biomedical Research ( IF 1.3 ) Pub Date : 2019-01-01 , DOI: 10.2220/biomedres.40.153
Yuuki Horii 1 , Takahiko Shiina 1, 2 , Saki Uehara 2 , Kanako Nomura 2 , Hiroki Shimaoka 1 , Kazuhiro Horii 1 , Yasutake Shimizu 1, 2, 3
Affiliation  

Cold-inducible RNA-binding protein (CIRBP) plays important roles in protection against harmful effects of cold temperature. We previously found that several splicing variants of CIRBP mRNA are constitutively expressed in the heart of non-hibernating euthermic hamsters and that one of the variants is predominantly expressed with remarkable reduction in the expression of other variants in hibernating hypothermic hamsters. The aim of this study was to determine whether the regulation of alternative splicing is a common function in a non-hibernator, the mouse. The expression of CIRBP mRNA was assessed by RT-PCR. In euthermic control mice, several splicing variants of CIRBP mRNA were detected in various organs. When hypothermia was induced in mice by using isoflurane anesthesia, the short form variant, which encodes full-length functional CIRBP, was predominantly detected. Keeping body temperature of anesthetized mice at 37°C prevented changes in the splicing pattern. Exposure of mice to a low temperature did not change the splicing pattern, suggesting that endogenous neuronal and/or humoral pathways activated in response to cold stimuli applied to the body surface play minor roles. In agreement with this, the shift in alternative splicing was reproduced in isolated leukocytes in vitro when they were incubated at 28°C. Since application of a TRPM8 or TRPA1 agonist at 37°C failed to promote the shift in the splicing pattern, it seems likely that cold-sensitive channels are not involved in the splicing regulation. Therefore, it is probable that a substantial reduction of temperature is a major cause of the regulation of alternative splicing of CIRBP transcripts. The regulatory system of CIRBP expression at the level of alternative splicing, which was originally discovered in the hibernating hamster, commonly exists in non-hibernators such as mice.

中文翻译:

体温过低会导致非冬眠小鼠(小鼠)中冷诱导RNA结合蛋白转录本的选择性剪接模式发生变化。

冷诱导RNA结合蛋白(CIRBP)在防止冷害方面起着重要作用。我们以前发现,CIRBP mRNA的几个剪接变异体在非冬眠性仓鼠的心脏中组成性表达,并且其中一个变异体主要表达为冬眠低温仓鼠中其他变异体的表达显着降低。这项研究的目的是确定替代剪接的调控是否在非冬眠小鼠中是常见功能。通过RT-PCR评估CIRBP mRNA的表达。在正常对照小鼠中,在各个器官中检测到了几种CIRBP mRNA的剪接变体。当通过异氟烷麻醉在小鼠体内引起体温过低时,编码全长功能性CIRBP的短形式变体 主要被检测到。将麻醉小鼠的体温保持在37°C,可以防止剪接模式发生变化。将小鼠暴露于低温下不会改变剪接模式,这表明响应于施加于体表的冷刺激而激活的内源性神经元和/或体液途径起着较小的作用。与此相符的是,当分离的白细胞在28℃温育时,在体外在分离的白细胞中复制了选择性剪接。由于在37°C下使用TRPM8或TRPA1激动剂不能促进剪接模式的转变,因此冷敏感通道似乎不参与剪接调控。因此,温度的大幅降低很可能是调节CIRBP转录本选择性剪接的主要原因。
更新日期:2019-11-01
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