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. 2011 Jun 1;90(3):430–440. doi: 10.1093/cvr/cvr097

Figure 2.

Figure 2

Mechanisms for regulation of epigenetics and gene expression by non-coding RNAs. NcRNAs can function as modulators of epigenetics through (A through C) chromatin remodelling or regulate gene expression at (D through F) transcriptional or (G through I) post-transcriptional level. (A) A 5′ domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3′ domain of HOTAIR binds the LSD1/CoREST/REST complex. This allows HOTAIR to coordinate histone H3 lysine 27 methylation and lysine 4 demethylation at the HOXD locus in trans. (B) In cis recruitment of PRC2 by Xist antisense RNA and appearance of H3K27me3 along the inactive X chromosome are among the earliest events in X inactivation. Recruitment of PRC1-mediated H2AK119ub1 parallels the recruitment of PRC2. (C) Similarly, antisense non-coding RNA ANRIL represses the expression from INK4b/ARF/INK4a locus by recruiting and retaining PRC1 and PRC2 complexes in cis. (D) LncRNA transcribed from the minor promoter of dihydrofolate reductase (DHFR) froms a triplex together with the transcription factor TFIIB and the major promoter leading to the dissociation of the preinitiation complex. (E) Enhancer region (i and ii) of Dlx5/6 generates an lncRNA Evf-2 which forms a complex with homeodomain protein Dlx-2 to activate transcription. (F) Transcription of B2 and Alu RNAs is induced upon heat-shock. They inhibit mRNA synthesis by disrupting contacts between RNA polymerase II and promoter DNA. (G) Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RNA-induced silencing complexes (RISCs) that target specific mRNAs for cleavage, translational repression or destabilization depending on the extent of sequence complementarity. (H) Natural antisense transcript (NAT) prevents the binding of the spliceosome to the 5′UTR of the Zeb2 mRNA. This leads to retention in an intron containing internal ribosomal entry site (IRES), which is dispensable for the translation of Zeb2 protein. (I) The nuclear trafficking of nuclear factor of activated T cells (NFAT) is inhibited by the interaction of non-coding repressor of NFAT (NRON) with proteins of the importin-beta superfamily.