The Working Modules of Long Noncoding RNAs in Cancer Cells
It is clear that RNA is more than just a messenger between gene and protein. The mammalian genome is pervasively transcribed, giving rise to tens of thousands of noncoding transcripts, especially long noncoding RNAs (lncRNAs). Whether all of these large t
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The Working Modules of Long Noncoding RNAs in Cancer Cells Ling Li and Xu Song
Abstract It is clear that RNA is more than just a messenger between gene and protein. The mammalian genome is pervasively transcribed, giving rise to tens of thousands of noncoding transcripts, especially long noncoding RNAs (lncRNAs). Whether all of these large transcripts are functional remains to be elucidated, but it is evident that there are many lncRNAs that seem not to be the “noise” of the transcriptome. Recent studies have set out to decode the regulatory role and functional diversity of lncRNAs in human physiological and pathological processes, and accumulating evidence suggests that most of the functional lncRNAs achieve their biological functions by controlling gene expression. In this chapter, we will organize these studies to provide a detailed description of the involvement of lncRNAs in the major steps of gene expression that include epigenetic regulation, RNA transcription, posttranscriptional RNA processing, protein translation, and posttranslational protein modification and highlight the molecular mechanisms through which lncRNAs function, involving the interactions between lncRNAs and other biological macromolecules. Keywords Long noncoding RNAs • Epigenome • Transcription • RNA spicing • Protein modification
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Introduction
A large range of biological processes involved in cancer progression, such as cell differentiation, proliferation, apoptosis, and metastasis, are widely reported to be associated with long noncoding RNAs (lncRNAs), which are thought to work in cis on neighboring genes or in trans to regulate distantly located genes or molecular targets in the nucleus and cytoplasm. It has been clear that lncRNAs can function through quite diverse mechanisms and that their interaction with DNA, RNA, or
L. Li • X. Song (*) Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan, China e-mail: [email protected]; [email protected] © Springer Science+Business Media Singapore 2016 E. Song (ed.), The Long and Short Non-coding RNAs in Cancer Biology, Advances in Experimental Medicine and Biology 927, DOI 10.1007/978-981-10-1498-7_2
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protein is a well-established action mode [1]. On the basis of the intermolecular interactions, most of the characterized lncRNAs are shown to function in gene expression control by acting as decoys, guides, or scaffolds [2, 3]. The “guiding” lncRNAs, like Kcnq1ot1 [4] and lincRNA-p21 [5], are associated with chromatin regulatory protein complexes or transcriptional co-regulators and recruit them to specific genomic DNA regions to regulate transcription; “decoying” lncRNAs, such as GAS5 [6], Lethe [7], and PANDA [8], mimic and compete with their consensus DNA-binding motifs for binding nuclear receptors or transcriptional factors in the nuclei; “scaffolding” lncRNAs, including HOTAIR [9], XIST [10], and NRON [11], bring specific regulatory proteins into proximity with each other to function as a unique complex. Furthermore, many lncRNAs are exclusively express
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