Long Noncoding RNAs with snoRNA Ends

Long Noncoding RNAs with snoRNA Ends
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DOI:
10.1016/j.molcel.2012.07.033
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发表时间:
2012-10-26
期刊:
影响因子:
16
通讯作者:
Chen, Ling-Ling
Chen, Ling-Ling
中科院分区:
生物学1区
文献类型:
--
作者:
Yin, Qing-Fei;Yang, Li;Chen, Ling-Ling

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我们描述了 sno-IncRNA 的发现,这是一类核富集的内含子衍生的长非编码 RNA (IncRNA),其两端均由 snoRNA 机器进行加工。在核酸外切修剪过程中,snoRNA 之间的序列不会被降解,导致侧翼为 snoRNA 序列但缺少 5' 帽和 3' Poly(A) 尾的 IncRNA 积累。此类 RNA 在细胞和组织中广泛表达,可由 box C/D 或 box H/ACA snoRNA 产生。重要的是,编码一类丰富的 sno-IncRNA (15q11-q13) 的基因组区域在普瑞德威利综合征 (PWS) 中被特异性删除。 PWS 区域 sno-IncRNA 不与核仁或卡哈尔体共定位,而是在其合成位点附近积累。这些 sno-IncRNA 与 Fox 家族剪接调节因子密切相关并改变剪接模式。因此,这些结果暗示 PWS 的分子发病机制中有一类以前未注释的 IncRNA。
We describe the discovery of sno-IncRNAs, a class of nuclear-enriched intron-derived long noncoding RNAs (IncRNAs) that are processed on both ends by the snoRNA machinery. During exonucleolytic trimming, the sequences between the snoRNAs are not degraded, leading to the accumulation of IncRNAs flanked by snoRNA sequences but lacking 5' caps and 3' poly(A) tails. Such RNAs are widely expressed in cells and tissues and can be produced by either box C/D or box H/ACA snoRNAs. Importantly, the genomic region encoding one abundant class of sno-IncRNAs (15q11-q13) is specifically deleted in Prader-Willi Syndrome (PWS). The PWS region sno-IncRNAs do not colocalize with nucleoli or Cajal bodies, but rather accumulate near their sites of synthesis. These sno-IncRNAs associate strongly with Fox family splicing regulators and alter patterns of splicing. These results thus implicate a previously unannotated class of IncRNAs in the molecular pathogenesis of PWS.