Figure 3 : The diverse functions of long intergenic non-coding RNAs (lincRNAs).

From: The functions and unique features of long intergenic non-coding RNA

Figure 3

a | Regulation of chromatin structure and function in cis and in trans. HOTTIP associates with the myeloid/lymphoid or mixed-lineage leukaemia protein 1 (MLL1) complex, which catalyses histone H3 Lys4 trimethylation (H3K4me3) to activate HOTTIP transcription in cis (left). HOTAIR interacts in trans with the polycomb recessive complex 2 (PRC2) to mediate its deposition of the repressive H3K27me3 modification and with the KDM1A–CoREST–REST complex to mediate H3K4 demethylation, to coordinate transcription repression at target loci (right)125. b,c | LincRNAs scaffold proteins and RNAs in the nucleus and cytoplasm. b | TINCR binds Staufen1 in the cytoplasm, and binds and stabilizes mRNAs through its TINCR box motif to promote epidermal differentiation48. c | In the presence of HuR, lincRNA-p21 is destabilized by recruitment of the microRNA (miRNA) let-7 in complex with Argonaute 2 (Ago2). HuR association with the lincRNA-p21 target mRNAs JUNB and CTNNB1 results in their translation. In the absence of HuR, lincRNA-p21 remains stable, accumulates and associates with the JUNB and CTNNB1 transcripts in a mechanism that is at least partially mediated by co-association with the RNA-binding protein Rck and represses their translation by decreasing their ribosome association71. d,e | LincRNAs act as protein and RNA decoys. d | The expression of the lincRNA Gas5 is induced by growth arrest. Gas5 mimics the glucocorticoid response element (GRE) and binds the DNA-binding domain of the glucocorticoid receptor (GR), which sequesters the glucocorticoid receptor from its target genes103. e | Linc-RoR is abundant in pluripotent stem cells, where it acts as a decoy of the miRNA miR-145, thereby inhibiting the targeting and downregulation of the mRNAs of the pluripotency factors octamer-binding protein 4 (OCT4), the transcription factor SOX2 and homeobox protein Nanog. As linc-RoR levels decrease during differentiation, miR-145 is released and mediates the degradation of its targets to promote differentiation106. Part a is from Ref. 125, Macmillan Publishers Limited.