Long Noncoding RNAs in Metabolic Syndrome Related Disorders

Figure 4

Biological role of lncRNAs. Role of lncRNAs has been implicated in the regulation of diverse processes, manifested by three ways of interactions: RNA-RNA, RNA-DNA, and RNA-protein, both in the nucleus and in the cytoplasm. (A) In the nucleus, lncRNAs have been shown to play a key role in imprinting control. lncRNAs may act as docking platforms for the chromatin remodeling complex, polycomb repressive complex (PRC2) 2 (e.g., HOTAIR), which methylates histone H3 at lysine 27 (H3K27me3) or with the heterogeneous group of Trithorax/MLL proteins (e.g., HOTTIP), leading to a repression or gain of transcriptional activity, respectively [8, 9]. (B) Other regulatory roles of lncRNAs in the nucleus include transcriptional regulation by interacting with transcription factors (e.g., PACER directly interacts with the repressive subunit of NF-κB, p50, thus preventing it from binding to the Cox-2 promoter [10]), heterogeneous nuclear ribonucleoproteins (hnRNPs) (e.g., THRIL, together with hnRNPL, acts as RNA-protein complex and binds to TNF-α promoter and mediates the induction of TNF-α expression [11]). (C) Moreover, lncRNAs may regulate the pre-mRNA alternative splicing (e.g., MALAT1), which acts as scaffold for SR proteins, present in nuclear speckles and modulates their phosphorylation [12]. In the cytosol, lncRNAs exert their function by interacting with target transcripts and miRNAs through base-pairing. (D) For miRNAs, lncRNAs may act as a molecular sponge, preventing specific miRNAs from binding to their target mRNAs (e.g., MIAT binds to miR-150-5p, thereby upregulating the level of miR-150-5p target gene). (E) lncRNA binding to mRNA may stabilize (e.g., BACE1-AS prevents miRNA-induced repression of BACE1 transcript) or decay target transcripts. (F) Moreover, lncRNAs promote (e.g., antisense Uchl1 interacts with Uchl1 mRNA, resulting in recruitment of ribosomes [13]) or repress (e.g., lincRNA-p21, which binds to target mRNA, causing recruitment of translation repressors [14]) translation of transcripts. This figure was produced using modified elements from the Servier Medical Art (http://www.servier.com/).