Sci Transl Med:肥胖元凶又增一员!这次是小RNA的研究新星“LincRNA”!

2018-06-24 Michael,Zoe 转化医学网

肥胖一直是个世界性的难题。随着肥胖人数的与日俱增,2型糖尿病和心血管疾病的罹患人数也在不断增加。研究脂质代谢目前已经成为机体代谢研究领域的重头戏。然而,目前人们对于脂质调控途径的认识并不能为临床减重提供足够的帮助。

导  读

肥胖一直是个世界性的难题。随着肥胖人数的与日俱增,2型糖尿病和心血管疾病的罹患人数也在不断增加。研究脂质代谢目前已经成为机体代谢研究领域的重头戏。然而,目前人们对于脂质调控途径的认识并不能为临床减重提供足够的帮助。随着全基因组关联研究(GWAS)的开展,研究人员发现肥胖或与一些非保守调控位点相关。LincRNA参与多种转录后修饰与表观遗传的调节,那是否参与脂质代谢的调节呢?最新的《Science Translational Medicine》给出了答案。

RNA领域的研究新星-LincRNA

LincRNA是目前RNA研究领域研究较为火热的非编码RNA,与mRNA相比,它的长度较短-大约只有200个核酸,同时具有组织特异性且表达量较低,参与多种代谢和疾病的调控。这种RNA主要通过转录后修饰和表观遗传学水平调控基因和蛋白质的表达。

目前,研究人员发现大约有1500种LincRNA参与鼠白色和褐色脂肪组织的调控。几百种LincRNA参与脂肪组织的分化过程。脂肪-LincRNA或许通过激活转录因子、组蛋白修饰和异质核糖核蛋白(hnRNPU)调节脂肪的分化。



人与小鼠LincRNA存在非保守性差异

由于小鼠与人类基因的相似性和小鼠组织的易获得性,研究人员一直将小鼠作为研究人体的模型材料。但来自两组转录组的系统分析显示啮齿类动物和人类的LincRNA存在非保守性差异,各种转录过程会产生组织特异性的LincRNA,那么这些新产生的RNA是否有功能呢?

Muredach P. Reilly率领研究团队对25名健康人进行了深度RNA测序(Deep RNA-seq),他们最终筛选出1001个脂肪相关性lincRNA(其中144个LincRNA从未发现),并将其称为“脂肪lincRNA”。同时研究人员发现这些lincRNA存在性别特异性表达的现象,例如linc-NUDT10表达与X染色体,其女性表达量远高于男性。同时,这些脂肪lincRNA还有种系差异。



脂肪LincRNA促进脂肪细胞分化!

研究人员继续筛选出120个(85个先前已发现,25个新近发现)LincRNA在脂肪组织中大量表达,同时通过免疫沉淀技术(ChIP)发现,这些lincRNA在组蛋白修饰标记物-H3K4me3, H3K4me1, and H3K27ac中大量聚集,显示出其较强的组蛋白修饰功能。

紧接着,研究人员发现了一种在脂肪组织大量聚集被称为Linc-ADAL的LincRNA,并通过免疫沉淀技术对其进行了功能测定,结果显示,这种LincRNA能够被一种称为PPAγ的蛋白调控,表达的Linc-ADAL与异质核糖核蛋白(hnRNPU)和类胰岛素生长因子2 mRNA结合蛋白2(IGF2BP2)相互作用,进而调控人体褐色脂肪组织的分化和人体的脂质代谢。



这些LincRNA存在何种意义呢?

总的来说,研究人员发现人类脂肪组织中大多数lincRNAs在小鼠中并不是保守,这些非保守脂肪lincRNA显示出PPARγ的调控活性,同时存在种族和性别差异性。 其发现的linc-ADAL是一种非保守的人类脂肪lincRNA,通过与不同的核和细胞质蛋白质相互作用调节脂肪细胞分化和脂质代谢。

一方面,本研究是对近期非保守性基因调控元件研究结果的进一步证实,另一方面,该研究有助于科研人员加强对脂质代谢和脂肪细胞分化的理解,使其更加明确肥胖背后复杂的调控机制。为下一步更深的研究和临床转化研究奠定了实验理论基础。



原始出处:Zhang X, Xue C, Lin J, et al. Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism. Sci Transl Med. 2018 Jun 20;10(446).

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    2019-05-06 zutt
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  4. 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GetPortalCommentsPageByObjectIdResponse(id=326554, encodeId=92e53265541c, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 24 08:42:18 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2019-04-25 bsmagic9140
  5. 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GetPortalCommentsPageByObjectIdResponse(id=326554, encodeId=92e53265541c, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 24 08:42:18 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-26 溜溜梅不酸

    学习了谢谢分享

    0

  6. 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    2018-06-25 花花1372
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  8. 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GetPortalCommentsPageByObjectIdResponse(id=326554, encodeId=92e53265541c, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 24 08:42:18 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-25 cici-moon

    不错的文章.值得深入研究

    0

  9. 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GetPortalCommentsPageByObjectIdResponse(id=326554, encodeId=92e53265541c, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 24 08:42:18 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-24 cqykthl

    肥胖是很多疾病元凶

    0

  10. 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GetPortalCommentsPageByObjectIdResponse(id=326554, encodeId=92e53265541c, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 24 08:42:18 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-24 张新亮1853311252142e2fm

    好文献学习了

    0

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