Blood:小核仁RNA,SNORD42A,对白血病细胞的生长和生存至关重要

2020-02-26 不详 MedSci原创

中心点:聚焦于snoRNA的CRISPR-CAS9筛选发现,SNORD42A对白血病细胞的增殖起到关键的调节作用。SNORD42A通过18S-U116 2'-O-甲基化调控核糖体生物发生和蛋白整体合成。摘要:非编码RNAs包括小核仁RNAs(snoRNAs),在白血病发生过程这具有重要作用,但其相关机制仍未完全明确。研究人员进行了聚焦于snoRNA的CRISPR-CAS9敲除文库筛选,该方法可靶向

中心点:

聚焦于snoRNA的CRISPR-CAS9筛选发现,SNORD42A对白血病细胞的增殖起到关键的调节作用。

SNORD42A通过18S-U116 2'-O-甲基化调控核糖体生物发生和蛋白整体合成。

摘要:

非编码RNAs包括小核仁RNAs(snoRNAs),在白血病发生过程这具有重要作用,但其相关机制仍未完全明确。研究人员进行了聚焦于snoRNA的CRISPR-CAS9敲除文库筛选,该方法可靶向所有的snoRNAnome及其主基因。

研究发现,在多重人白血病细胞系中,含有C/D盒的SNORD42A是AML细胞存在和增殖的一个至关重要的调控因子。在细胞系中,SNORD42A在原发性AML患者样本中持续表达,表达水平高于CD34+祖细胞、单核细胞和粒细胞。

在功能上,SNORD42A缺失可减弱集落形成能力,并抑制增殖。SNORD42A作为一个C/D盒snpRNA,指导18S rRNA的116位鸟苷上的2'-O-甲基化。

敲除SNORD42A可减弱18S-U116 2'-O-甲基化,这与核糖体蛋白翻译的特异性减少有关。

在细胞系中,SNORD42A缺失的白血病细胞的体积缩小。

综上所述,本研究证实,与U116 18S rRNA 2'-O-甲基化相伴的SNORD42A的高表达对白血病细胞的生长和生存至关重要。

原始出处:


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    2020-07-31 huagfeg
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    2021-01-11 zsyan
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