Dynamic Change and Target Prediction of Axon-Specific MicroRNAs in Regenerating Sciatic Nerve.
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 neuro-degeneration 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.
Nemours Biomedical Research, Alfred I DuPont Hospital for Children, Wilmington, Delaware, United States of America; Department of Biological Sciences, University of Delaware, Delaware, Newark, United States of America.
Monichan
M
Phay
Nemours Biomedical Research, Alfred I DuPont Hospital for Children, Wilmington, Delaware, United States of America.
Hak Hee
HH
Kim
Nemours Biomedical Research, Alfred I DuPont Hospital for Children, Wilmington, Delaware, United States of America.
Soonmoon
S
Yoo
D000818:Animals; D001369:Axons; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology*; D017423:Sequence Analysis, RNA
D035683:MicroRNAs