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Nat Commun：发现TERRA是维持端粒结构所必需的

2016-08-22 佚名 生物谷

TERRA端粒结构
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尽管端粒具有特别紧凑和难以接近的结构，但是它们像DNA剩余部分一样发生转录。由端粒转录产生的长链非编码RNA被称作TERRA，而且它们的功能是保持这些保护性结构所必不可少的。这是来自西班牙国家癌症研究中心（Spanish National Cancer Research Centre, CNIO）的Maria A. Blasco团队在一项新的研究中得出的结论。他们也确定了人基因组上产生这些分子的位


尽管端粒具有特别紧凑和难以接近的结构，但是它们像DNA剩余部分一样发生转录。由端粒转录产生的长链非编码RNA被称作TERRA，而且它们的功能是保持这些保护性结构所必不可少的。这是来自西班牙国家癌症研究中心（Spanish National Cancer Research Centre, CNIO）的Maria A. Blasco团队在一项新的研究中得出的结论。他们也确定了人基因组上产生这些分子的位置。相关研究结果于2016年8月17日在线发表在Nature Communications期刊上，论文标题为“Telomeric RNAs are essential to maintain telomeres”。

这一发现与Blasco团队两年前的观察结果相一致。在那时候，他们研究了小鼠细胞，并且观察到保护它们的20条染色体的TERRA主要起源自18号染色体对，而且在较小程度上起源自9号染色体。

在这项新的研究中，Blasco团队证实在人体内，这些RNA独自地起源自一个位点上。他们尽可能地分析了之前提出的18种RNA，但是只有起源自20号染色体长臂（20q）和X染色体短臂（Xp）上的那些RNA表现出TERRA特征。

为了证实来自这两个位点的这些RNA确实是TERRA，Blasco团队利用CRISPR-Cas9技术剔除这两个基因座位。他们随后注意到抑制Xp并不产生重大的后果，但是抑制20q对端粒产生显著的负面影响。

研究人员写道，“鉴别出20q是人TERRA产生的一个主要位点允许我们解决TERRA在端粒生物学中的作用。”在多种细胞系中剔除这个位点后，他们观察到DNA和端粒损伤显著增加，同时染色体不稳定性也在增加。

这次首次证实TERRA在保护端粒中发挥的至关重要作用存在于任何一种有机体中。Blasco解释道，“这些结果是引人注目的，这是因为它们明确地证实TERRA在细胞活力和保护端粒中发挥着一种必不可少的作用；它们在端粒上发挥的作用与端粒酶或保护端粒的shelterin蛋白发挥的作用一样重要。”

发现20q区域是TERRA的来源和证实这些RNA在保护端粒中发挥的关键作用为研究检测到这种染色体区域发生变化的某些综合征打开大门。它也为研究患有在端粒酶或shelterin蛋白上没有发生这些变化的端粒失调症的病人提供新的途径。

原始出处

Juan José Montero, Isabel López de Silanes, Osvaldo Graña & Maria A. Blasco.Telomeric RNAs are essential to maintain telomeres.Nat Commun.2016

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    2017-06-16 仁心济世

    #Nat#

    0

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    2017-03-03 liuli5079

    #COMMUN#

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    2016-12-02 surilei

    #ERR#

    0

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    2016-08-22 oo902

    厉害的研究

    0