Dynamic Change and Target Prediction of Axon-Specific MicroRNAs in Regenerating Sciatic Nerve
Date
2015-09-02
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PLOS (Public Library of Science)
Abstract
Injury to axons in the peripheral nervous system induces rapid and local regenerative
responses to form a new growth cone, and to generate a retrogradely transporting injury signal.
The evidence for essential roles of intra-axonal protein synthesis during regeneration is
now compelling. MicroRNA (miRNA) has recently been recognized as a prominent player in
post-transcriptional regulation of axonal protein synthesis. Here, we directly contrast temporal
changes of miRNA levels in the sciatic nerve following injury, as compared to those in
an uninjured nerve using deep sequencing. Small RNAs (<200 nucleotides in length) were
fractionated from the proximal nerve stumps to improve the representation of differential
miRNA levels. Of 141 axoplasmic miRNAs annotated, 63 rat miRNAs showed significantly
differential levels at five time points following injury, compared to an uninjured nerve. The
differential changes in miRNA levels responding to injury were processed for hierarchical
clustering analyses, and used to predict target mRNAs by Targetscan and miRanda. By
overlapping these predicted targets with 2,924 axonally localizing transcripts previously
reported, the overlapping set of 214 transcripts was further analyzed by the Gene Ontology
enrichment and Ingenuity Pathway Analyses. These results suggest the possibility that
the potential targets for these miRNAs play key roles in numerous neurological functions
involved in ER stress response, cytoskeleton dynamics, vesicle formation, and neurodegeneration
and-regeneration. Finally, our results suggest that miRNAs could play a direct
role in regenerative response and may be manipulated to promote regenerative ability of
injured nerves.
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Phay M, Kim HH, Yoo S (2015) Dynamic Change and Target Prediction of Axon-Specific MicroRNAs in Regenerating Sciatic Nerve. PLoS ONE 10(9): e0137461. doi:10.1371/journal. pone.0137461