Lisse Thomas S, Adams John S, Hewison Martin
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, 50 Blossom St., Thier 11, Boston, MA 02114, USA.
Crit Rev Eukaryot Gene Expr. 2013;23(3):195-214. doi: 10.1615/critreveukaryotgeneexpr.2013007147.
MicroRNAs (miRNAs) are short noncoding RNAs that orchestrate complex posttranscriptional regulatory networks essential to the regulation of gene expression. Through complementarity with messenger RNA (mRNA) sequences, miRNAs act primarily to silence gene expression through either degradation or inhibited translation of target transcripts. In this way, miRNAs can act to fine-tune the transcriptional regulation of gene expression, but they may also play distinct roles in the proliferation, differentiation, and function of specific cell types. miRNA regulatory networks may be particularly important for signaling molecules such as vitamin D that exert pleiotropic effects on tissues throughout the body. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) functions as a steroid hormone that, when bound to its nuclear vitamin D receptor, is able to regulate target gene expression. However, recent studies have also implicated 1,25(OH)2D in epigenetic regulation of genes most notably as a modulator of miRNA function. The current review details our understanding of vitamin D and miRNAs with specific emphasis on the implications of this interaction for biological responses to vitamin D in one of its classical target tissues, i.e., bone.
微小RNA(miRNA)是短链非编码RNA,它们构建了对基因表达调控至关重要的复杂转录后调控网络。通过与信使RNA(mRNA)序列互补,miRNA主要通过降解靶转录本或抑制其翻译来使基因表达沉默。通过这种方式,miRNA可以微调基因表达的转录调控,但它们也可能在特定细胞类型的增殖、分化和功能中发挥独特作用。miRNA调控网络对于诸如维生素D等对全身组织发挥多效性作用的信号分子可能尤为重要。维生素D的活性形式1,25-二羟基维生素D(1,25(OH)2D)作为一种类固醇激素发挥作用,当与核维生素D受体结合时,能够调节靶基因表达。然而,最近的研究也表明1,25(OH)2D参与基因的表观遗传调控,最显著的是作为miRNA功能的调节剂。本综述详细阐述了我们对维生素D和miRNA的理解,特别强调了这种相互作用对维生素D在其经典靶组织之一即骨骼中的生物学反应的影响。