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诱导生长期毛囊发育过程中依赖于Dicer和凸起干细胞的微小RNA

Dicer- and Bulge Stem Cell-Dependent MicroRNAs During Induced Anagen Hair Follicle Development.

作者信息

Vishlaghi Neda, Lisse Thomas S

机构信息

Department of Biology, University of Miami, Coral Gables, FL, United States.

Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, United States.

出版信息

Front Cell Dev Biol. 2020 May 14;8:338. doi: 10.3389/fcell.2020.00338. eCollection 2020.

Abstract

MicroRNAs (miRNAs) are a major class of conserved non-coding RNAs that have a wide range of functions during development and disease. Biogenesis of canonical miRNAs depend on the cytoplasmic processing of pre-miRNAs to mature miRNAs by the Dicer endoribonuclease. Once mature miRNAs are generated, the miRNA-induced silencing complex (miRISC), or miRISC, incorporates one strand of miRNAs as a template for recognizing complementary target messenger RNAs (mRNAs) to dictate post-transcriptional gene expression. Besides regulating miRNA biogenesis, Dicer is also part of miRISC to assist in activation of the complex. Dicer associates with other regulatory miRISC co-factors such as activation responsive RNA-binding protein 2 (Tarbp2) to regulate miRNA-based RNA interference. Although the functional role of miRNAs within epidermal keratinocytes has been extensively studied within embryonic mouse skin, its contribution to the normal function of hair follicle bulge stem cells (BSCs) during post-natal hair follicle development is unclear. With this question in mind, we sought to ascertain whether Dicer-Tarpb2 plays a functional role within BSCs during induced anagen development by utilizing conditional knockout mouse models. Our findings suggest that Dicer, but not Tarbp2, functions within BSCs to regulate induced anagen (growth phase) development of post-natal hair follicles. These findings strengthen our understanding of miRNA-dependency within hair follicle cells during induced anagen development.

摘要

微小RNA(miRNA)是一类主要的保守非编码RNA,在发育和疾病过程中具有广泛的功能。经典miRNA的生物合成依赖于Dicer核糖核酸内切酶将前体miRNA在细胞质中加工成成熟的miRNA。一旦产生成熟的miRNA,miRNA诱导沉默复合体(miRISC)就会将其中一条miRNA链纳入,作为识别互补靶信使RNA(mRNA)的模板,从而决定转录后基因表达。除了调节miRNA生物合成外,Dicer也是miRISC的一部分,有助于激活该复合体。Dicer与其他调节性miRISC辅助因子如激活反应性RNA结合蛋白2(Tarbp2)结合,以调节基于miRNA的RNA干扰。尽管miRNA在表皮角质形成细胞中的功能作用已在胚胎小鼠皮肤中得到广泛研究,但其在出生后毛囊发育过程中对毛囊隆突干细胞(BSC)正常功能的贡献尚不清楚。考虑到这个问题,我们试图通过利用条件性敲除小鼠模型来确定Dicer-Tarpb2在诱导生长期发育过程中是否在BSC中发挥功能作用。我们的研究结果表明,Dicer而非Tarbp2在BSC中发挥作用,以调节出生后毛囊的诱导生长期(生长阶段)发育。这些发现加深了我们对诱导生长期发育过程中毛囊细胞内miRNA依赖性的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d2f/7240072/3255a697513b/fcell-08-00338-g001.jpg

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