Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin

Jin Young Kim; Seon-Young Han; Kiho Sung; Jeong Yeon Seo; Cheol Hwan Myung; Chan Song Jo; Jee Hoe Yoon; Ji Yun Park; Jae Sung Hwang

doi:10.4062/biomolther.2022.167

Biomolecules & Therapeutics https://doi.org/10.4062/biomolther.2022.167

Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin

Jin Young Kim¹, Seon-Young Han², Kiho Sung², Jeong Yeon Seo², Cheol Hwan Myung¹, Chan Song Jo¹, Jee Hoe Yoon¹, Ji Yun Park¹ and Jae Sung Hwang^1,*

¹Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104,
²OliPass Cosmeceuticals Company, Youngin 17015, Republic of Korea

^*E-mail: jshwang@khu.ac.kr
Tel: +82-31-201-3797, Fax: +82-31-203-4969

Received: December 19, 2022; Revised: February 22, 2023; Accepted: March 2, 2023; Published online: March 27, 2023.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract: Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA). To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.; Keywords: Exon skipping, Melanosome transport, Melanophilin (Mlph), Peptide nucleic acid (PNA), Synaptotagmin-like preotein homology domain (SHD)

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