Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin.

Autor: Kim JY; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea., Han SY; OliPass Cosmeceuticals Company, Youngin 17015, Republic of Korea., Sung K; OliPass Cosmeceuticals Company, Youngin 17015, Republic of Korea., Seo JY; OliPass Cosmeceuticals Company, Youngin 17015, Republic of Korea., Myung CH; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea., Jo CS; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea., Yoon JH; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea., Park JY; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea., Hwang JS; Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Youngin 17104, Republic of Korea.
Jazyk: angličtina
Zdroj: Biomolecules & therapeutics [Biomol Ther (Seoul)] 2023 Jul 01; Vol. 31 (4), pp. 466-472. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.4062/biomolther.2022.167
Abstrakt: 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.
Databáze: MEDLINE