Table 2Function classification of lncRNAs.Signal ��Some lncRNAs have been reported to respond to diverse stimuli, hinting they may act as molecular signals [12, 24, 25, 27, 35]. For example, selleck screening library lncRNAs can act as markers for imprinting (Air and Kcnq1ot1), X inactivation (Xist), and silencing (COOLAIR). ChIP-Seq studies showed that the gene-activating enhancers produce lncRNA transcripts (eRNAs) [29, 95], and their expression level positively correlates with that of nearby genes, indicating a possible role in regulating mRNA synthesis. This is supported by a recent Loss-of-Function study that found the knockdown of 7 out of 12 lncRNAs affects expression of their cognate neighboring genes [8]. Decoy ��lncRNA can function as molecular decoy to negatively regulate an effector.

Gas5 contains a hairpin sequence motif that resembles the DNA-binding site of the glucocorticoid receptor [31]. It can serve as a decoy to release the receptor from DNA to prevent transcription of metabolic genes [14]. Another example is the telomeric repeat-containing RNA (TERRA). It interacts with the telomerase protein through a repeat sequence complementary to the template sequence of telomerase RNA [11, 34].Guide ��Upon interaction with the target molecular, lncRNA may have the ability to guide it into the proper position either in cis (on neighboring genes) or in trans (on distantly located genes). The newly found eRNAs appear to exert their effects in cis by binding to specific enhancers and actively engaged in regulating mRNA synthesis [11, 29].

HOTAIR and HOTTIP are transcribed within the human HOX clusters, and serve as signals of anatomic positions by expressing in cells that have distal and posterior positional Entinostat identities; they both require the interacting partners to be properly localized to the site of action [6]. In this process, chromosomal looping of the 5�� end of HOXA brings HOTTIP into the spatial proximity of multiple HOXA genes, enforcing the maintenance of H3K4me3 and gene activation [14]. This long-range gene activation mechanism suggests that chromosome looping plays a central role in delivering lncRNA to its site of action [11, 45].Scaffold ��Recent studies found that several lncRNAs have the capacity to bind more than two protein partners, where the lncRNAs serve as adaptors to form the functional protein complexes. The telomerase RNA TERC (TERRA) is a classic example of RNA scaffold, and is essential for telomerase function. HOTAIR binds the polycomb complex PRC2 to exert its ��signal�� function. A recent study found that the 3,700nt of HOTAIR also interact with a second complex consisting of LSD1, CoREST, and REST to antagonize gene activation, further emphasizing its important role as the scaffold of the functional complex [11, 51].