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mTORC1和肌肉再生是由LINC00961编码的SPAR多调节的

Akinobu Matsumoto¹, Alessandra Pasut¹, Masaki Matsumoto²

¹Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

|December 27, 2016

概括

研究人员发现了一种隐藏的多,SPAR,由长非编码RNALINC00961编码. 通过氨基酸调节mTORC1的激活,这对于受伤后的肌肉再生至关重要.

科学领域:

分子生物学
遗传学
细胞生物学

背景情况:

长非编码RNAs (lncRNAs) 越来越多地被认为具有超出非编码作用的功能.
一些lncRNA含有小的开放读取 (ORF),可以转化为功能性多.
这些 lncRNA编码的多的生物学意义在很大程度上仍未被探索.

研究的目的:

识别和功能性描述由lncRNA LINC00961编码的新型多.
阐明该多在细胞信号通路和组织再生中的作用.

主要方法:

来自LINC00961的新型聚酸 (SPAR) 的鉴定和特征.
生物化学测试以确定SPAR局部化和相互作用 (例如与v-ATPase).
编辑CRISPR/Cas9基因以创建特定于SPAR的淘汰老鼠模型.
在急性损伤后评估肌肉再生的体内研究.

主要成果:

从LINC00961中鉴定出一种保存的多,局部存在于晚期内分体/溶解体中.
它与v-ATPase相互作用,并对氨基酸刺激的mTORC1激活产生负面调节.
在SPAR淘汰赛中,小鼠表现出增强的mTORC1激活和受伤后改善的肌肉再生.
在骨肌肉受伤后,LncRNA LINC00961的表达下调.

结论:

一种新型的lncRNA编码多,它提供了一个微调mTORC1激活的机制,以响应氨基酸的可用性.
这一途径对于受伤后有效的肌肉再生至关重要.
lncRNA可以编码小聚,调节基本的生物过程,以满足特定组织的需求.

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