Interaction and cross-talk between non-coding RNAs

Abstract

Non-coding RNA (ncRNA) has been shown to regulate diverse cellular processes and functions through controlling gene expression. Long non-coding RNAs (lncRNAs) act as a competing endogenous RNAs (ceRNAs) where microRNAs (miRNAs) and lncRNAs regulate each other through their biding sites. Interactions of miRNAs and lncRNAs have been reported to trigger decay of the targeted lncRNAs and have important roles in target gene regulation. These interactions form complicated and intertwined networks. Certain lncRNAs encode miRNAs and small nucleolar RNAs (snoRNAs), and may regulate expression of these small RNAs as precursors. SnoRNAs have also been reported to be precursors for PIWI-interacting RNAs (piRNAs) and thus may regulate the piRNAs as a precursor. These miRNAs and piRNAs target messenger RNAs (mRNAs) and regulate gene expression. In this review, we will present and discuss these interactions, cross-talk, and co-regulation of ncRNAs and gene regulation due to these interactions.

Keywords: Circular RNA; Competing endogenous RNA; Interaction; Long non-coding RNA; MicroRNA; PIWI-interacting RNAs; Small nucleolar RNA.

Fig. 1

Representative interactions and cross-talk between non-coding RNAs. A Interaction and co-regulation between circular RNA, ciRS-7 (CDR1as), and miRNAs. (a) ciRS-7 (CDR1as) contains more than 60 binding sites for miR-7. A mismatch at the central part of the binding region prevents miRNA-mediated cleavage. Thus, ciRs-7 acts as a sponge for miR-7 and increase levels of miR-7 targets [40, 41]. (b) MiR-671 binds to ciRS-7 in a sequence-specific manner and suppresses ciRS-7 expression and function [48]. B Interactions and co-regulation between lncRNA H19 and miRNAs. (a) MiR-141 binds to H19 in a sequence-specific manner and suppresses H19 expression and its oncogenic function [107]. (b) H19 functions as a ceRNA for miR-138 and miR-200a, and reduces suppression of their targets Vimentin, ZEB1, and ZEB2 [108]. (c) MiR-675 which is encoded by H19 targets mRNAs of oncogenes and functions as a tumor suppressor [82, 109]. C LncRNA SNHG5 encodes SNORD50A and SNORD50B which inhibit KRAS function. Expression of these snoRNAs may be dependent on the host lncRNA, SNHG5, and expression [90]. D HBII-239 (SNORD71) encodes miRNAs. Expression of these miRNAs may depend on the expression of the host snoRNA, HBII-239 (SNORD71). The C/D box snoRNA HBII-239 (SNORD71)-derived miRNA precursors bind to fibrillarin protein, a component of a nucleolar small nuclear ribonucleoprotein (snRNP) [94]. E LncRNA GAS5 encodes snoRNAs that generate piwi-interacting RNAs, piRNAs. Pi-snoRNA 75, a piRNA, activates tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) [97]