Gene activation-associated long noncoding RNAs function in mouse preimplantation development.
Gene activation-associated long noncoding RNAs function in mouse preimplantation development.
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DOI：
10.1242/dev.116996
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Imamura T
中科院分区：
文献类型：
--
作者：
Hamazaki N;Uesaka M;Nakashima K;Agata K;Imamura T
在小鼠中，合子激活发生在各种各样的基因，主要是在2细胞阶段。长链非编码RNA（lncRNA）越来越多地被认为是基因表达的调节因子。在这项研究中，MII卵母细胞和2-细胞胚胎的定向RNA-seq鉴定了1000多个不同转录的lncRNA/mRNA基因对。这些双向启动子相关非编码RNA（pancRNA）的表达与其同源基因的上调密切相关。相反，敲低三种丰富的pancRNA导致mRNA表达减少，伴随着持续的DNA甲基化，即使在存在负责DNA去甲基化的酶的情况下。特别是，在1细胞阶段显微注射针对白细胞介素17 d（IL 17 d）mRNA的丰富pancRNA伴侣的siRNA导致胚胎死亡，这是通过在4细胞阶段在体外提供IL 17 D蛋白来挽救的。因此，这类新的lncRNA可以顺式调节转录机制以激活合子基因，并且对于植入前发育是重要的。突出显示的文章：在小鼠胚胎早期合子基因激活过程中，启动子相关的非编码RNA可以促进其伴侣mRNA的表达，这可能对正常发育很重要。
In mice, zygotic activation occurs for a wide variety of genes, mainly at the 2-cell stage. Long noncoding RNAs (lncRNAs) are increasingly being recognized as modulators of gene expression. In this study, directional RNA-seq of MII oocytes and 2-cell embryos identified more than 1000 divergently transcribed lncRNA/mRNA gene pairs. Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes. Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation. In particular, microinjection of siRNA against the abundant pancRNA partner of interleukin 17d (Il17d) mRNA at the 1-cell stage caused embryonic lethality, which was rescued by supplying IL17D protein in vitro at the 4-cell stage. Thus, this novel class of lncRNAs can modulate the transcription machinery in cis to activate zygotic genes and is important for preimplantation development. Highlighted article: During zygotic gene activation in the early mouse embryo, promoter-associated noncoding RNAs can promote expression of their partner mRNAs, which may be important for normal development.
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影响因子：
4.8
作者：
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通讯作者：
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