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KMID : 0606920230310040466
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Biomolecules & Therapeutics
2023 Volume.31 No. 4 p.466 ~ p.472
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Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin
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Kim Jin-Young
Han Seon-Young
Sung Ki-Ho
Seo Jeong-Yeon
Myung Cheol-Hwan
Jo Chan-Song
Yoon Jee-Hoe
Park Ji-Yun
Hwang Jae-Sung
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Abstract
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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.
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KEYWORD
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Exon skipping, Melanosome transport, Melanophilin (Mlph), Peptide nucleic acid (PNA), Synaptotagmin-like preotein homology domain (SHD)
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