Recent Application of Intronic MicroRNA Agents in Cosmetics

Abstract

Utilization of gene silencing effectors, such as microRNA (miRNA) and small hairpin RNA (shRNA), provides a powerful new strategy for human skin care in vivo, particularly for hyperpigmentation treatment and aging prevention. For example, tyrosinase (Tyr), a melanocytic membrane-bound glycoprotein, is the rate-limiting enzyme critical for melanin (black pigment) biosynthesis in skins and hairs. There are over 54 native microRNA capable of targeting human tyrosinase for skin whitening and lightening. In this study, we have designed a mir-434-5p homologue and used it to successfully demonstrate the feasibility of miRNA-mediated skin whitening in vitro and in vivo. Under the same experimental condition in trials, Pol-II-directed intronic mir-434-5p expression did not cause any detectable sign of cytotoxicity, whereas siRNAs targeting the same sequence induced certain non-specific mRNA degradation as previously reported. Because the intronic miRNA-mediated gene silencing pathway is tightly regulated by multiple intracellular surveillance systems, including Pol-II transcription, RNA splicing, exosome digestion and NMD processing, the current findings underscore the fact that intronic miRNA agents, such as mir-434-5p homologues, are effective, target-specific and safe to be used for skin whitening without any overt cytotoxic effect. Given that the human skins also express a variety of native miRNAs, we may re-design these miRNAs based on their individual functions for skin care, which will provide significant insights into areas of opportunity for new cosmetic interventions.Keywords microRNA (miRNA), intronic microRNA (Id-miRNA), mir-434-5p, tyrosinase (Tyr), hyaluronidase (Hyal), RNA interference (RNAi), skin whitening, antiaging, cosmetics.S.-Y. Ying (ed.) Current Perspectives in microRNAs (miRNA), 51

A multiplexed miRNA and transgene expression platform for simultaneous repression and expression of protein coding sequences

“…65 It has been suggested that intronic pri-miRNAs are processed by spliceosome components; whereas, intergenic pri-miRNAs are processed by Drosha-like RNases in the nucleus yielding pre-miRNAs. 66 Coupled-expression of a transgene such as GFP from the same transcription unit with RNAi permits the use of the natural miRNA platform to simultaneously promote RNAi induced knockdown of target genes and overexpress a transgene. Although GFP was used as a proof-of-concept transgene in this study which also allowed easy monitoring of the transfected cells, any other transgene including drug resistance genes, marker genes, transcriptional activators, or therapeutic genes could be used in place of GFP.…”

Genome-wide development of miRNA-based SSR markers in Cleistogenes songorica and analysis of their transferability to Gramineae/non-Gramineae species

“…Endogenous small RNAs have essential roles in plant development, phase transition (Khraiwesh et al 2012) and gene expression under diverse stress conditions, including biotic and abiotic stress conditions, and in different developmental stages of the life cycle (Ganie and Mondal 2015;Singh et al 2017). Like small nucleolar RNAs (snoRNAs), short interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), miRNAs are not translated into proteins but are often involved in the regulation of gene expression (Lin et al 2008;Neilson and Sharp 2008). miRNAs are highly conserved in both plants and animals and have been found in plants, green algae, viruses, fungi, and older lineages of animals (Bartel and Bartel 2003;Saini et al 2008).…”

Genome-wide development of miRNA-based SSR markers in Cleistogenes songorica with their transferability analysis to gramineae and non- gramineae species

“…Endogenous small RNAs have essential roles in plant development, phase transition (Khraiwesh et al 2012) and gene expression under diverse stress conditions, including biotic and abiotic stress conditions, and in different developmental stages of the life cycle Singh et al 2017). Like small nucleolar RNAs (snoRNAs), short interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), miRNAs are not translated into proteins but are often involved in the regulation of gene expression (Lin et al 2008;Neilson and Sharp 2008). miRNAs are highly conserved in both plants and animals and have been found in plants, green algae, viruses, fungi, and older lineages of animals (Bartel and Bartel 2003;Saini et al 2008).…”