Effects of age and hindlimb immobilization and remobilization on fast troponin T precursor mRNA alternative splicing in rat gastrocnemius muscle.
Effects of age and hindlimb immobilization and remobilization on fast troponin T precursor mRNA alternative splicing in rat gastrocnemius muscle.
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DOI：
10.1139/apnm-2015-0381
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Kimball SR
中科院分区：
文献类型：
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作者：
Ravi S;Schilder RJ;Berg AS;Kimball SR
骨骼肌快速肌钙蛋白T（TNNT 3）是骨骼肌收缩机制的重要组成部分。编码TNNT 3的前体mRNA是可变剪接的，并且TNNT 3剪接形式表达模式的变化与肌肉收缩期间细丝钙敏感性和力产生的改变相关，从而调节肌肉功能。有趣的是，在衰老过程中，肌肉力量/横截面积减少，这表明质量损失并不能完全解释衰老过程中出现的肌肉功能受损。因此，在本研究中，我们测试的假设，年龄和肌肉负荷的变化与大鼠腓肠肌中TNNT 3选择性剪接的改变有关。我们发现，在2、9和18个月大的大鼠中，几种TNNT 3剪接形式的相对丰度随年龄的变化而显着变化，并且该模式与体重而不是肌肉质量的变化相关。后肢固定7天导致剪接形式相对丰度的显著改变，使得模式与在较轻动物中观察到的模式相似。7天的再运动恢复了非固定肢体中观察到的剪接模式，即使肌肉质量尚未开始恢复。总之，结果表明TNNT 3前mRNA选择性剪接响应于施加在肌肉上的负荷的变化而快速（即在数天内）调节。此外，结果表明，TNNT 3选择性剪接恢复到对照模式是在肌肉质量增加之前开始的。
Fast skeletal muscle Troponin T (TNNT3) is an important component of the skeletal muscle contractile machinery. The pre-mRNA encoding TNNT3 is alternatively spliced and changes in the pattern of TNNT3 splice form expression are associated with alterations in thin filament calcium sensitivity and force production during muscle contraction, thereby regulating muscle function. Interestingly, during aging, muscle force/cross sectional area is reduced, suggesting that loss of mass does not completely account for the impaired muscle function that develops during the aging process. Therefore, in the present study, we tested the hypothesis that age- and changes in muscle loading are associated with alterations in TNNT3 alternative splicing in the rat gastrocnemius muscle. We found that the relative abundance of several TNNT3 splice forms varied significantly with age among 2, 9, and 18-month old rats, and the pattern correlated with changes in body weight rather than muscle mass. Hindlimb immobilization for 7 days resulted in dramatic alterations in splice form relative abundance such that the pattern was similar to that observed in lighter animals. Remobilization for 7 days restored the splicing pattern toward that observed in the non-immobilized limb, even though muscle mass had not yet begun to recover. In conclusion, the results suggest that TNNT3 pre-mRNA alternative splicing is rapidly (i.e. within days) modulated in response to changes in the load placed on the muscle. Moreover, the results show that restoration of TNNT3 alternative splicing to control patterns is initiated prior to an increase in muscle mass.