Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat
Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat
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DOI：
10.1038/nature11508
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发表时间：
2012-11-15
期刊：
影响因子：
64.8
通讯作者：
Gustincich, Stefano
中科院分区：
文献类型：
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作者：
Carrieri, Claudia;Cimatti, Laura;Gustincich, Stefano
大多数哺乳动物基因组都是转录的（1-3）。这就产生了大量的转录本，包括蛋白质编码信使rna、长链非编码rna （lncRNAs）和重复序列，如SINEs（短穿插核元件）。很大比例的ncrna具有未知功能的核富集(4)。反义lncRNAs可与另一条链上的蛋白质编码基因配对，形成正反义对，调控表观遗传沉默、转录和mRNA稳定性（5-10）。在这里，我们发现了一个核富集的lncRNA反义小鼠泛素羧基末端水解酶L1 (Uchl1)，一个涉及脑功能和神经退行性疾病的基因（11）。反义Uchl1在转录后水平上增加Uchl1蛋白的合成，从而鉴定出一个新的功能lncrna类别。反义Uchl1的活性依赖于59个重叠序列和内嵌的倒置SINEB2元件的存在。这些特征是其他天然反义转录物所共有的，可以赋予对绿色荧光蛋白的人工反义调节活性。反义Uchl1的功能受应激信号通路的控制，因为雷帕霉素抑制mTORC1会导致Uchl1蛋白的增加，这与反义Uchl1 RNA从细胞核转运到细胞质有关。反义Uchl1 RNA则需要重叠的义蛋白编码mRNA与活性多聚体结合以进行翻译。这些数据揭示了另一层基因表达控制在转录后水平。
Most of the mammalian genome is transcribed(1-3). 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(4). 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(5-10). Here we identify a nuclear-enriched lncRNA antisense to mouse ubiquitin carboxyterminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases(11). 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 59 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.