Long noncoding RNAs: Functional surprises from the RNA world

Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Genes & development (Impact Factor: 12.64). 08/2009; 23(13):1494-504. DOI: 10.1101/gad.1800909
Source: PubMed

ABSTRACT Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs with little or no protein-coding capacity. Although the vast majority of long noncoding RNAs have yet to be characterized thoroughly, many of these transcripts are unlikely to represent transcriptional "noise" as a significant number have been shown to exhibit cell type-specific expression, localization to subcellular compartments, and association with human diseases. Here, we highlight recent efforts that have identified a myriad of molecular functions for long noncoding RNAs. In some cases, it appears that simply the act of noncoding RNA transcription is sufficient to positively or negatively affect the expression of nearby genes. However, in many cases, the long noncoding RNAs themselves serve key regulatory roles that were assumed previously to be reserved for proteins, such as regulating the activity or localization of proteins and serving as organizational frameworks of subcellular structures. In addition, many long noncoding RNAs are processed to yield small RNAs or, conversely, modulate how other RNAs are processed. It is thus becoming increasingly clear that long noncoding RNAs can function via numerous paradigms and are key regulatory molecules in the cell.

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    • "lncRNAs target chromatin modification enzymes to add 'tags' to chromatin: the chromatin tags in turn are targeted by protein, small and large RNAs. The Polycomb system proteins (PCGPs), that methylate histones over short (Müller and Kassis 2006) or long (Lee et al. 2006; Schwartz et al. 2006; Wang and Chang 2011) distances, are targeted by direct binding to promoters or repressors or recruited to chromatin by lncRNAs which bind both PGCPs and either other proteins or other RNAs (Khalil et al. 2009; Nagano and Fraser 2011; Wilusz et al. 2009). Although Polycomb is usually associated with gene repression, in some cases it has been recruited to gene activation pathways (Gao et al. 2014). "
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    G3-Genes Genomes Genetics 07/2015; DOI:10.1534/g3.115.019943 · 2.51 Impact Factor
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    • "Although some lncRNAs are transcribed by RNA polymerase III (Dieci et al. 2007; Kapranov et al. 2007) or produced by partial processing by the snoRNA machinery (Yin et al. 2012; Zhang, Yin, et al. 2014), the majority of lncRNAs shows a clear signature of RNA polymerase II transcription, with the promoters marked by histone H3 lysine 4 trimethylation (H3K4me3) and the transcribed gene bodies marked by histone H3 lysine 36 trimethylation (H3K36me3) (Guttman et al. 2009; Khalil et al. 2009). Although most lncRNAs have not been functionally characterized , those that have been suggest lncRNAs are versatile molecules that can interact with DNA, other RNAs and proteins , either through nucleotide base pairing or through formation of structural domains generated by RNA folding (Wilusz et al. 2009; Poliseno et al. 2010; Salmena et al. 2011; Wang and Chang 2011). As expected for regulatory molecules, lncRNAs display specific spatiotemporal expression patterns, high tissue specificity (Cabili et al. 2011; Djebali et al. 2012; Pauli et al. 2012; Li et al. 2014; Necsulea et al. 2014; Washietl et al. 2014) and can regulate expression of genes in close genomic proximity (cis-acting) or at distance (trans-acting) (Mercer et al. 2009; Ponting et al. 2009; Rinn and Chang 2012; Ulitsky and Bartel 2013). "
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