肌萎缩侧索硬化症小鼠骨骼肌中 microRNA 生物发生机制和 microRNA/RNA 比值的失调。
Dysregulation of microRNA biogenesis machinery and microRNA/RNA ratio in skeletal muscle of amyotrophic lateral sclerosis mice.
机构信息
Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong, Australia.
Australian Institute for Bioengineering and Nanotechnology, Australia Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
出版信息
Muscle Nerve. 2018 May;57(5):838-847. doi: 10.1002/mus.26039. Epub 2017 Dec 22.
INTRODUCTION
The pathology of amyotrophic lateral sclerosis (ALS) is associated with impaired RNA processing and microRNA (miRNA) dysregulation. Here we investigate the regulation of the members of the miRNA biogenesis pathways and total miRNA levels at different stages of the disease.
METHODS
Muscle, brain, and spinal cord tissue were obtained from presymptomatic, symptomatic, and end-stage superoxide dismutase 1 (SOD1) mice. miRNA and transcript levels were measured by quantitative polymerase chain reaction.
RESULTS
As the diseases progresses, several genes involved in miRNA biogenesis as well as the miRNA/total RNA (totRNA) ratio increased in the tibialis anterior (TA) muscle but not in the soleus or in neural tissue.
DISCUSSION
We propose that a dysregulation in the miRNA/totRNA ratio in the TA muscle from SOD1 mice reflects a pathological increase in miRNA biogenesis machinery. Alterations in the miRNA/totRNA ratio influence the levels of reference noncoding RNAs and may therefore potentially compromise the accuracy of commonly used miRNA normalization strategies. Muscle Nerve 57: 838-847, 2018.
简介
肌萎缩侧索硬化症（ALS）的病理学与 RNA 加工受损和 microRNA（miRNA）失调有关。在这里，我们研究了 miRNA 生物发生途径成员的调节以及疾病不同阶段的总 miRNA 水平。
方法
从超氧化物歧化酶 1（SOD1）小鼠的无症状、有症状和终末期获得肌肉、大脑和脊髓组织。通过定量聚合酶链反应测量 miRNA 和转录物水平。
结果
随着疾病的进展，几种参与 miRNA 生物发生的基因以及 miRNA/总 RNA（totRNA）比值在前胫骨肌（TA）中增加，但在比目鱼肌或神经组织中没有增加。
讨论
我们提出，SOD1 小鼠 TA 肌肉中 miRNA/totRNA 比值的失调反映了 miRNA 生物发生机制的病理性增加。miRNA/totRNA 比值的改变影响参考非编码 RNA 的水平，因此可能潜在地影响常用 miRNA 归一化策略的准确性。肌肉神经 57：838-847，2018。
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