MicroRNA-25 functions in regulation of pigmentation by targeting the transcription factor MITF in alpaca (Lama pacos) skin melanocytes

Zhu, Z.; He, J.; Jia, X.; Jiang, J.; Bai, R.; Yu, X.; Lv, L.; Fan, R.; He, X.; Geng, J.; You, R.; Dong, Y.; Qiao, D.; Lee, K.-B.; Smith, G.W.; Dong, C.

doi:10.1016/j.domaniend.2009.10.004

« PreviousDomestic Animal Endocrinology
Volume 38, Issue 3 , Pages 200-209, April 2010

MicroRNA-25 functions in regulation of pigmentation by targeting the transcription factor MITF in alpaca (Lama pacos) skin melanocytes

Z. Zhu
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
J. He
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
X. Jia
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
J. Jiang
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
R. Bai
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
X. Yu
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
L. Lv
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
R. Fan
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
X. He
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
J. Geng
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
R. You
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
Y. Dong
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
D. Qiao
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
K.-B. Lee
- Laboratory of Mammalian Reproductive Biology and Genomics, Departments of Animal Science and Physiology, Michigan State University, East Lansing, MI 48824, USA
G.W. Smith
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
- Laboratory of Mammalian Reproductive Biology and Genomics, Departments of Animal Science and Physiology, Michigan State University, East Lansing, MI 48824, USA
C. Dong
- College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China
- Corresponding author at: College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, China. Tel.: +86 354 6288208; fax: +86 354 6288208.

Received 18 August 2009; received in revised form 25 September 2009; accepted 21 October 2009. published online 28 December 2009.

Abstract

Although the influence of endocrine factors is well established, the molecular and cellular mechanisms controlling coat color are not completely understood. A major mechanism for post-transcriptional regulation of gene expression is through the action of microRNAs (miRNAs), which anneal to the 3’ untranslated region of mRNAs in a sequence-specific fashion and either block translation or promote transcript degradation. In this study, we investigated the expression of miRNAs in the skin of alpacas with brown vs white coat color using a microarray screen; identified potential mRNA targets for identified miRNAs among coat color genes; and subsequently determined the ability of a specific, differentially expressed miRNA (miR-25) to suppress expression of micropthalmia-associated transcription factor (MITF), a predicted miR-25 target gene that regulates genes linked to coat color. Expression of 10 different miRNA species in the skin of alpacas with brown vs white coat color was identified from microarray screens. Of the 10 alpaca skin miRNAs identified, predicted binding sites in the 3′ untranslated region of RNAs encoding for known genes linked to coat color were primarily for miR-25, but sites were also identified for miR-129 and miR-377. Potential miR-25 binding sites were present in transcripts encoding for 11 coat color genes, including MITF. An inverse relationship between transcript abundance for MITF and miR-25 was observed in skin samples collected from alpacas with white vs brown coat color. Furthermore, overexpression of miR-25 in cultured melanocytes reduced MITF mRNA and protein abundance and corresponding mRNA abundance for the MITF-regulated enzymes tyrosinase and tyrosinase-related protein 1. Results support a novel functional role for miRNA-25 in the regulation of gene expression linked to coat color.

Keywords: Alpaca, Coat color, Gene expression, Melanocyte, Micropthalmia-associated transcription factor, MicroRNA-25, Skin