Mild hypothermia causes a shift in the alternative splicing of cold-inducible RNA-binding protein transcripts in Syrian hamsters
Mild hypothermia causes a shift in the alternative splicing of cold-inducible RNA-binding protein transcripts in Syrian hamsters
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DOI：
10.1152/ajpregu.00012.2019
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发表时间：
2019-08-01
影响因子：
2.8
通讯作者：
Shimizu, Yasutake
中科院分区：
文献类型：
--
作者：
Horii, Yuuki;Shimaoka, Hiroki;Shimizu, Yasutake
冷休克蛋白被认为与冬眠动物的耐寒性有关。我们以前证明，选择性剪接可能允许快速诱导仓鼠心脏中的功能性冷诱导RNA结合蛋白（CIRBP）。本研究的目的是确定叙利亚仓鼠选择性剪接的主要原因。RT-PCR分析表明，CIRBP mRNA组成型表达在心脏，脑，肺，肝，和肾脏的非冬眠的常温仓鼠与几个选择性剪接变异。与此相反，含有功能性CIRBP的开放阅读框的短变体主要在冬眠动物中发现。将动物保持在寒冷和黑暗的环境中并没有引起选择性剪接的变化。通过给予腺苷A（1）受体激动剂诱导体温降低，复制了剪接模式的转变。然而，当体温保持在37摄氏度时，激动剂不能改变模式，这表明中央腺苷A（1）受体与选择性剪接的改变没有直接联系。通过异氟烷麻醉结合冷却将体温快速降低至10 ℃并没有改变剪接模式，但维持轻度低温（类似于28 ℃）2 h引起模式的转变。结果表明，动物需要保持在轻度低温足够的时间来诱导选择性剪接的转变。这适用于自然冬眠，因为进入冬眠的仓鼠显示体温逐渐下降，保持在轻度低温几个小时。
Cold-shock proteins are thought to participate in the cold-tolerant nature of hibernating animals. We previously demonstrated that an alternative splicing may allow rapid induction of functional cold-inducible RNA-binding protein (CIRBP) in the hamster heart. The purpose of the present study was to determine the major cause of the alternative splicing in Syrian hamsters. RT-PCR analysis revealed that CIRBP mRNA is constitutively expressed in the heart, brain, lung, liver, and kidney of nonhibernating euthermic hamsters with several alternative splicing variants. In contrast, the short variant containing an open-reading frame for functional CIRBP was dominantly found in the hibernating animals. Keeping the animals in a cold and dark environment did not cause a shift in the alternative splicing. Induction of hypothermia by central administration of an adenosine A(l)-receptor agonist reproduced the shift in the splicing pattern. However, the agonist failed to shift the pattern when body temperature was kept at 37 degrees C, suggesting that central adenosine A(1) receptors arc not directly linked to the shift of the alternative splicing. Rapid reduction of body temperature to 10 degrees C by isoflurane anesthesia combined with cooling did not alter the splicing pattern, but maintenance of mild hypothermia (similar to 28 degrees C) for 2 h elicited the shift in the pattern. The results suggest that animals need to be maintained at mild hypothermia for an adequate duration to induce the shift in the alternative splicing. This is applicable to natural hibernation because hamsters entering hibernation show a gradual decrease in body temperature, being maintained at mild hypothermia for several hours.