4.1. Cellular Functions selleck chem inhibitor of lncRNAWith thousands of lncRNAs identified in mammals and other vertebrates [16], a few lncRNAs have been extensively studied, which have shed light on their possible functions. Firstly, lncRNAs are involved in various epigenetic regulations through recruitment of chromatin remodeling complexes to specific genomic loci, such as Xist, Air, and Kcnq1ot1 [22, 43]. Secondly, lncRNAs can regulate gene expression by interacting with protein partners in biological processes like protein synthesis, imprinting (Kcnq1ot1, Air), cell cycle control (TERRA), alternative splicing (MALAT1), and chromatin structure regulation (DNMT3b, PANDA) [9, 10, 38, 71, 85�C89]. Thirdly, lncRNAs are involved in enhancer-regulating gene activation (eRNAs), in which cases they may interact directly with distal genomic regions [90].

Fourthly, some lncRNAs serve as interacting partners or precursors for short regulatory ncRNAs [91]. For example, microRNAs (miRNAs) can be generated through sequential cleavage of lncRNAs, while Piwi-interacting RNAs (piRNAs) can be produced by processing a single lncRNA transcript [88]. Recent studies have shown the expression of lncRNA is tissue specific. Loewer et al. studied the expression of lncRNA in global remodeling of the epigenome and during reprogramming of somatic cells to induce pluripotent stem cells (iPSCs). They found some lncRNAs have cell-type specific expression pattern [26, 92]. Loss-of-function studies on most intergenic lncRNAs expressed in mouse embryonic stem (ES) cells revealed that knockdown of intergenic lncRNAs has major consequences on gene expression patterns, which are comparable to the effects of knockdown of well-known ES cell regulators [93].

This indicated that lncRNAs might play important roles in regulating developmental process. The ENCODE project analyzed the tissue-specific expression of lncRNAs in 31 cell types, and found that many lncRNAs have brain-specific expression pattern [9, 12]. There are increasing lines of evidences that link dysregulations of lncRNAs to diverse human diseases ranging from neuron diseases to cancer [9, 10], suggesting that the involvement of lncRNAs in human diseases can be far more prevalent than previously thought [94].4.2. Molecular Mechanisms of lncRNAThe precise mechanism of how lncRNAs function still remains largely unknown.

Currently, there are several hypothesis about it, including (1) RNA:DNA:DNA triplex (trans-); (2) RNA:DNA hybrid; (3) RNA:RNA hybrid of lncRNA with a nascent transcript; (4) RNA-protein interaction (cis-/trans-). Although only (1), (2), and (4) have been experimentally Anacetrapib demonstrated so far [14], it is generally thought that lncRNAs may function through the interaction with its partners, such as DNA, RNA, or protein, and serve the following roles: signal, decoy, scaffold, and guide [11, 14].