TY - JOUR
T1 - Detection of 1α,25-dihydroxyvitamin D-regulated miRNAs in zebrafish by whole transcriptome sequencing
AU - Craig, Theodore A.
AU - Zhang, Yuji
AU - Magis, Andrew T.
AU - Funk, Cory C.
AU - Price, Nathan D.
AU - Ekker, Stephen C.
AU - Kumar, Rajiv
PY - 2014/6/1
Y1 - 2014/6/1
N2 - The sterol hormone, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), regulates gene expression and messenger RNA (mRNA) concentrations in zebrafish in vivo. Since mRNA concentrations and translation are influenced by micro-RNAs (miRNAs), we examined the influence of 1α,25(OH)2D3 on miRNA expression in zebrafish in vivo with whole transcriptome RNA sequencing, searched for miRNA binding sites in 1α,25(OH)2D 3-sensitive genes, and performed correlation analyses between 1α,25(OH)2D3-sensitive miRNAs and mRNAs. In vehicle-and 1α,25(OH)2D3-treated, 7-day postfertilization larvae, between 282 and 295 known precursor miRNAs were expressed, and in vehicle-and 1α,25(OH)2D3-treated fish, between 83 and 122 novel miRNAs were detected. Following 1α,25(OH)2D3 treatment, 31 precursor miRNAs were differentially expressed (p<0.05). The differentially expressed miRNAs are predicted to potentially alter mRNAs for metabolic enzymes, transcription factors, growth factors, and Jak-STAT signaling. We verified the role of a 1α,25(OH)2D3-sensitive miRNA, miR125b, by demonstrating alterations in the concentrations of the mRNA of a 1α,25(OH)2D3-regulated gene, Cyp24a1, following transfection of renal cells with a miR125b miRNA mimic. Changes in the Cyp24a1 mRNA concentration by the miR125b miRNA mimic were associated with changes in the protein for Cyp24a1. Our data show that 1α,25(OH)2D 3 regulates miRNA in zebrafish larvae in vivo and could thereby influence vitamin D-sensitive mRNA concentrations.
AB - The sterol hormone, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), regulates gene expression and messenger RNA (mRNA) concentrations in zebrafish in vivo. Since mRNA concentrations and translation are influenced by micro-RNAs (miRNAs), we examined the influence of 1α,25(OH)2D3 on miRNA expression in zebrafish in vivo with whole transcriptome RNA sequencing, searched for miRNA binding sites in 1α,25(OH)2D 3-sensitive genes, and performed correlation analyses between 1α,25(OH)2D3-sensitive miRNAs and mRNAs. In vehicle-and 1α,25(OH)2D3-treated, 7-day postfertilization larvae, between 282 and 295 known precursor miRNAs were expressed, and in vehicle-and 1α,25(OH)2D3-treated fish, between 83 and 122 novel miRNAs were detected. Following 1α,25(OH)2D3 treatment, 31 precursor miRNAs were differentially expressed (p<0.05). The differentially expressed miRNAs are predicted to potentially alter mRNAs for metabolic enzymes, transcription factors, growth factors, and Jak-STAT signaling. We verified the role of a 1α,25(OH)2D3-sensitive miRNA, miR125b, by demonstrating alterations in the concentrations of the mRNA of a 1α,25(OH)2D3-regulated gene, Cyp24a1, following transfection of renal cells with a miR125b miRNA mimic. Changes in the Cyp24a1 mRNA concentration by the miR125b miRNA mimic were associated with changes in the protein for Cyp24a1. Our data show that 1α,25(OH)2D 3 regulates miRNA in zebrafish larvae in vivo and could thereby influence vitamin D-sensitive mRNA concentrations.
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U2 - 10.1089/zeb.2013.0899
DO - 10.1089/zeb.2013.0899
M3 - Article
C2 - 24650217
AN - SCOPUS:84902305132
SN - 1545-8547
VL - 11
SP - 207
EP - 218
JO - Zebrafish
JF - Zebrafish
IS - 3
ER -