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内含子 microRNA 与其宿主基因的共表达揭示了 miR-483-5p 作为 IGF2 伴侣的潜在作用。

Coexpression of an intronic microRNA and its host gene reveals a potential role for miR-483-5p as an IGF2 partner.

机构信息

Harbin Medical University, Harbin, China.

出版信息

Mol Cell Endocrinol. 2011 Feb 10;333(1):96-101. doi: 10.1016/j.mce.2010.11.027. Epub 2010 Dec 10.

Abstract

MicroRNAs (miRNAs) are endogenous noncoding RNAs that downregulate gene expression by inhibiting translation or promoting mRNA degradation. Although over one-third of miRNAs are located within the intronic regions of transcription units, the expression of such "intron-derived" (or "intronic") miRNAs and their relationship with their host gene remain a mystery. Here, we show that miR-483-5p, which is located within the second intron of the insulin-like growth factor (Igf2) gene, is downregulated in mouse Hepa1-6 cells in a direct correlation with the Igf2 transcript by chromeceptin, an inhibitor of Igf2 at the transcriptional level. Furthermore, miR-483-5p overexpression and knockdown regulates the suppressor of cytokine signalling 3 (Socs3) and Igf2 mRNAs, respectively. Finally, Socs3, a key putative leptin-resistant factor in obesity, is identified as a direct target of miR-483-5p. These data suggest that miR-483-5p can be coexpressed together with its host gene, Igf2, and revealed the link between this miRNA and the IGF2 growth factor. In addition, these observations not only provide supporting evidence for the codependent expression of intronic miRNAs and their host genes in vitro, but also give insight into the role of miR-483-5p in metabolism regulation and tumourigenesis.

摘要

微小 RNA(miRNAs)是内源性非编码 RNA,通过抑制翻译或促进 mRNA 降解来下调基因表达。尽管超过三分之一的 miRNAs 位于转录单元的内含子区域内,但这些“内含子衍生”(或“内含子”)miRNAs 的表达及其与宿主基因的关系仍然是一个谜。在这里,我们表明 miR-483-5p 位于胰岛素样生长因子(Igf2)基因的第二个内含子内,通过 chromeceptin(一种转录水平上抑制 Igf2 的抑制剂)在 Hepa1-6 细胞中与 Igf2 转录物呈直接负相关下调。此外,miR-483-5p 的过表达和敲低分别调节细胞因子信号转导抑制因子 3(Socs3)和 Igf2 mRNA。最后,肥胖症中关键的瘦素抵抗因子 Socs3 被鉴定为 miR-483-5p 的直接靶标。这些数据表明,miR-483-5p 可以与其宿主基因 Igf2 一起共表达,并揭示了这种 miRNA 与 IGF2 生长因子之间的联系。此外,这些观察结果不仅为内含子 miRNA 与其宿主基因在体外的共依赖性表达提供了支持证据,也为 miR-483-5p 在代谢调节和肿瘤发生中的作用提供了新的见解。

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