nature20121115-6

一个国际研究小组获得了一个可以提高工业蛋白质合成用于治疗用途的新发现。他们设法了解了非蛋白质编码RNA的一个新功能:借助这类称作“反义”非编码RNA的活性可以提高编码基因的蛋白质合成活性。

-2012年11月15日《自然》

中文翻译


【题目】新型非编码反义RNA也能够促进蛋白表达

【译文】哺乳动物基因组中的大多数基因可被转录。这产生了大量转录本,包括编码蛋白的信使RNA、长的非编码RNA(lncRNAs)和重复序列,例如SINE(短的散布核元件)。大部分ncRNAs在核内丰富,且功能未知。反义lncRNAs或许可以通过与互补链上编码蛋白的基因组成正义-反义对,以调控表观遗传沉默、转录和mRNA稳定性。本研究鉴定了鼠泛素化羧基端水解酶L1 (Uchl1)(一种参与脑功能和神经变性疾病基因)的一种核内含量丰富的反义lncRNA。反义Uchl1可在转录后水平增加UCHL1蛋白的合成,因而鉴定了一类具有新功能的lncRNA。反义Uchl1活性取决于5′重叠序列的出现和一种嵌入的反向SINEB2元件。这些特征与其他自然反义转录本共有,并能承担对绿色荧光蛋白的人工反义调控活性。反义Uchl1功能受到压力信号通路的控制,因为雷帕霉素的mTORC1抑制作用会引起与反义Uchl1 RNA从核到胞质穿梭运动相关的UCHL1蛋白增加。反义Uchl1 RNA是将重叠正义的编码蛋白mRNA与翻译的有效多核糖体相联系所必需的。这些数据揭示了转录后水平基因表达控制的另一个层面。

英文原稿


[Title]: Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat

[Authors]:Claudia Carrieri,1, 11 Laura Cimatti,1, 11 Marta Biagioli,1, 2 Anne Beugnet,3 Silvia Zucchelli,1, 2 Stefania Fedele,1 Elisa Pesce,3 Isidre Ferrer,4 Licio Collavin,5, 6 Claudio Santoro,7 Alistair R. R. Forrest,8 Piero Carninci,8 Stefano Biffo,3, 9 Elia Stupka10 & Stefano Gustincich1, 2

[Abstract]Most of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function. Antisense lncRNAs may form sense–antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability. Here we identify a nuclear-enriched lncRNA antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases. Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 5′ overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural antisense transcripts and can confer regulatory activity to an artificial antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.

原文地址

http://www.nature.com/nature/journal/v491/n7424/full/nature11508.html

 

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