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

Aaron P. Russell*, Lobna Ghobrial, Shyuan Ngo, Justin Yerbury, Evelyn Zacharewicz, Roger Chung, Séverine Lamon

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)838-847
    Number of pages10
    JournalMuscle and Nerve
    Volume57
    Issue number5
    Early online date22 Dec 2017
    DOIs
    Publication statusPublished - May 2018

    Keywords

    • ALS
    • Biogenesis
    • MicroRNA
    • Noncoding RNA
    • Normalization
    • Skeletal muscle

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