Dysregulation of microRNA biogenesis machinery and microRNA/RNA ratio in skeletal muscle of amyotrophic lateral sclerosis mice. Issue 5 (22nd December 2017)

• Record Type: Journal Article
• Authors: Russell, Aaron P.; Ghobrial, Lobna; Ngo, Shyuan; Yerbury, Justin; Zacharewicz, Evelyn; Chung, Roger; Lamon, Séverine
• Is Part Of: Muscle & nerve. Volume 57:Issue 5(2018)
• Page Start: 838
• Page End: 847
• Publication Date: 2017-12-22
• Subjects: ALS -- biogenesis -- microRNA -- noncoding RNA -- normalization -- skeletal muscle; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.26039
• Languages: English
• ISSNs: 0148-639X

Abstract

ABSTRACT: 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) G93A 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 G93A 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