Fig. 1.4 ); for example, they can bind to regions of chromatin, restricting RNA polymerase access to coding genes within the region. The best-known example of a repressive function involves XIST, which is transcribed from the X chromosome and plays an essential role in physiologic X chromosome inactivation. XIST itself escapes X inactivation, but forms a repressive “cloak” on the X chromosome from which it is transcribed, resulting in gene silencing. Conversely, it has been appreciated that many enhancers are sites of lncRNA synthesis, with the lncRNAs expanding transcription from gene promoters through http://ebooksmedicine.net
Unwinding of miRNA duplex
Fig. 1.3 Generation of microRNAs (miRNA) and their mode of action in regulating gene function. miRNA genes are transcribed to produce a primary miRNA (pri-miRNA), which is processed within the nucleus to form premiRNA composed of a single RNA strand with secondary hairpin loop structures that form stretches of double-stranded RNA. After this premiRNA is exported out of the nucleus via specific transporter proteins, the cytoplasmic enzyme Dicer trims the pre-miRNA to generate mature double-stranded miRNAs of 21 to 30 nucleotides. The miRNA subsequently unwinds, and the resulting single strands are incorporated into the multiprotein RISC. Base pairing between the single-stranded miRNA and its target mRNA directs RISC to either cleave the mRNA target or to repress its translation. In either case, the target mRNA gene is silenced posttranscriptionally.
A. Gene activation Ribonucleoprotein transcription complex
Decoy lncRNAB. Gene suppression Gene suppression
C. Promote chromatin modification
Methylation,
D. Assembly of protein complexes
Fig. 1.4 Roles of long noncoding RNAs (lncRNAs). (A) Long noncoding RNAs (lncRNAs) can facilitate transcription factor binding and thus promote gene activation. (B) Conversely, lncRNAs can preemptively bind transcription factors and thus prevent gene transcription. (C) Histone and DNA modification by acetylases or methylases (or deacetylases and demethylases) may be directed by the binding of lncRNAs. (D) In other instances lncRNAs may act as scaffolding to stabilize secondary or tertiary structures and/or multisubunit complexes that influence general chromatin architecture or gene activity.
(Adapted from Wang KC, Chang HY: Molecular mechanisms of long noncoding RNAs, Mol Cell 43:904, 2011.) a variety of mechanisms (
Fig. 1.4 ). Ongoing studies are exploring the role of lncRNAs in diseases like atherosclerosis and cancer.