Unlinking an lncRNA from Its Associated cis Element.
Unlinking an lncRNA from Its Associated cis Element.
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DOI：
10.1016/j.molcel.2016.02.029
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发表时间：
2016-04-07
期刊：
影响因子：
16
通讯作者：
Weiss MJ
中科院分区：
文献类型：
--
作者：
Paralkar VR;Taborda CC;Huang P;Yao Y;Kossenkov AV;Prasad R;Luan J;Davies JO;Hughes JR;Hardison RC;Blobel GA;Weiss MJ
长链非编码rna （lnc）可以调控基因表达和蛋白质功能。然而，在哺乳动物细胞中表达的数千种lncrna中，具有生物活性的lncrna所占比例存在争议。我们研究了Lockd (Cdkn1b下游的LncRNA)，这是一个434 nt的多聚腺苷化LncRNA，起源于Cdkn1b基因的4千碱基（kb） 3 '。在红系细胞系中，缺失25 kb的Lockd位点可使Cdkn1b转录减少约70%。相比之下，在Lockd转录起始位点下游80 bp处插入一个聚腺苷化盒，将整个lncRNA转录水平降低了约90%，而对Cdkn1b转录没有影响。Lockd启动子包含一个dna酶超敏感位点，结合许多转录因子，在染色体构象捕获研究中与Cdkn1b启动子物理关联。因此，Lockd基因通过类似增强子的顺式元件正向调节Cdkn1b的转录，而lncRNA本身是可缺性的，其他lncRNA可能也是如此。编码lncRNA的基因座是通过lncRNA转录物还是DNA元件发挥作用，通常并不清楚。pararkar等人提供了一个模型来剖析这些贡献，并表明Lockd lncRNA基因的5 '区域含有邻近Cdkn1b基因的增强子，而Lockd lncRNA对于Cdkn1b的表达是必不可少的。
Long non-coding (lnc) RNAs can regulate gene expression and protein functions. However, the proportion of lncRNAs with biological activities among the thousands expressed in mammalian cells is controversial. We studied Lockd (LncRNA downstream of Cdkn1b), a 434 nt polyadenylated lncRNA originating 4 kilobases (kb) 3′ to the Cdkn1b gene. Deletion of the 25 kb Lockd locus reduced Cdkn1b transcription by approximately 70% in an erythroid cell line. In contrast, homozygous insertion of a polyadenylation cassette 80 bp downstream of the Lockd transcription start site reduced the entire lncRNA transcript level by > 90%, with no effect on Cdkn1b transcription. The Lockd promoter contains a DNase hypersensitive site, binds numerous transcription factors, and physically associates with the Cdkn1b promoter in chromosomal conformation capture studies. Thus, the Lockd gene positively regulates Cdkn1b transcription through an enhancer-like cis element, while the lncRNA itself is dispensable, which may be the case for other lncRNAs. Whether loci encoding lncRNAs function via their lncRNA transcripts or DNA elements is often unclear. Paralkar et al. provide a model for dissecting these contributions and show that the 5′ region of the Lockd lncRNA gene contains an enhancer for the neighboring Cdkn1b gene, while Lockd lncRNA is dispensable for Cdkn1b expression.