Title

Dysregulation of microRNA biogenesis machinery and microRNA/RNA ratio in skeletal muscle of amyotrophic lateral sclerosis mice

RIS ID

127076

Publication Details

Russell, A. P., Ghobrial, L., Ngo, S., Yerbury, J., Zacharewicz, E., Chung, R. & Lamon, S. (2018). Dysregulation of microRNA biogenesis machinery and microRNA/RNA ratio in skeletal muscle of amyotrophic lateral sclerosis mice. Muscle & Nerve, 57 (5), 838-847.

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 SOD1G93A 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.

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Link to publisher version (DOI)

http://dx.doi.org/10.1002/mus.26039