Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.
Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.
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Linc-RAM 通过调节糖原磷酸化酶活性促进肌细胞分化
DOI：
10.1186/s13619-022-00109-8
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发表时间：
2022-03-07
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhai L;Wan X;Wu R;Yu X;Li H;Zhong R;Zhu D;Zhang Y
长链非编码RNA（lncRNA）是多种生物学过程，尤其是骨骼肌细胞分化的重要调控因子。目前发现的大多数lncRNA定位于细胞核中，在基因表达中起调节作用。细胞质lncRNA的了解较少。我们以前确定了一个长的基因间非编码RNA（linc-RNA）肌生成激活剂（Linc-RAM），直接结合MyoD在细胞核中，以增强肌肉细胞分化。在这里，我们报告说，一个相当大的部分Linc-RAM定位于肌细胞的细胞质中。为了探索细胞质Linc-RAM的分子功能，我们试图鉴定Linc-RAM结合蛋白。我们在这里报告，Linc-RAM与糖原磷酸化酶（PYGM）在细胞质中的物理相互作用。PYGM的敲除可显著减弱Linc-RAM促进肌细胞分化的功能。功能丧失和功能获得试验表明PYGM以酶活性依赖性方式增强肌细胞分化。最后，我们表明，Linc-RAM和PYGM之间的相互作用正调控肌肉细胞中PYGM的酶活性。总的来说，我们的研究结果揭示了细胞质Linc-RAM通过调节PYGM活性促进肌细胞分化的分子机制。我们的研究结果表明，在肌细胞分化过程中，lncRNA和细胞代谢之间存在串扰。
Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes, especially skeletal muscle cell differentiation. Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression. The cytoplasmic lncRNAs are less well understood. We previously identified a long intergenic non-coding RNA (linc-RNA) activator of myogenesis (Linc-RAM) that directly binds MyoD in the nucleus to enhance muscle cell differentiation. Here, we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells. To explore the molecular functions of cytoplasmic Linc-RAM, we sought to identify Linc-RAM-binding proteins. We report here that Linc-RAM physically interacts with glycogen phosphorylase (PYGM) in the cytoplasm. Knockdown ofPYGMsignificantly attenuates the function of Linc-RAM in promoting muscle cell differentiation. Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner. Finally, we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells. Collectively, our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity. Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.
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DOI：
10.1042/bj20111416
发表时间：
2012-02-01
期刊：
The Biochemical journal
影响因子：
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作者：
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DOI：
10.1016/j.tig.2017.11.005
发表时间：
2018-03
期刊：
Trends in genetics : TIG
影响因子：
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DOI：
10.1046/j.1432-1327.1999.00058.x
发表时间：
1999-02-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
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Wang, ZX