RNA templating the epigenome

Abstract

C ellular pathways must be synergized, -controlled and organized to manage homeostasis. To achieve high selectivity within the crowded cellular milieu the cell utilizes scaffolding complexes whose role is to bring molecules in proximity thereby controlling and enhancing intermolecular interactions and signaling events. To date, scaffolds have been shown to be composed of proteinaceous units; however, recent evidence has supported the idea that non-coding RNAs may also play a similar role. In this Pointof-View article we discuss recent data on ncRNA scaffolds, with particular focus on ncRNA HOTAIR. Using our current knowledge of signaling networks we discuss the role that RNA may play in writing and regulating histone modifications and the information needed for correct gene expression. Further, we speculate on additional, yet undiscovered, roles that ncRNAs may be playing as molecular scaffolds.

Polycomb repressive complex 1 activities determine the columnar organization of motor neurons

“…One possibility is that Bmi1 acts as a limiting factor that can grossly raise or lower the overall activity of PRC1, while additional factors are responsible for the graded activity of the complex over the rostrocaudal axis. One candidate for such a partner is a long noncoding RNA (lncRNA), which appears to regulate PRC binding at several loci, including Hox clusters (Spitale et al 2011). Differential transcription of such an RNA over the rostrocaudal axis could have the effect of grading PRC recruitment to Hox loci.…”

HOTAIR: a cancer-related long non-coding RNA

“…They could regulate gene expression and function, including dosage compensation [15,16], genome rearrangement [17], chromatin modifications [7,18,19], gene imprinting [20,21,22], alternative splicing [23], nuclear-cytoplasmic trafficking [24,25,26], cell cycle control [27,28,29] and inactivation of major tumor suppressor genes [30,31]. Wang et al [32] summarized the functions of lncRNAs as signals [33], decoys [34,35], guides [15] and scaffolds [18,36].…”

“…Moreover, recent studies have indicated that lncRNAs participated in a wide range of biological pathways and cellular processes. They could regulate gene expression and function, including dosage compensation [15,16] [18,36].…”

“…Moreover, recent studies have indicated that lncRNAs participated in a wide range of biological pathways and cellular processes. They could regulate gene expression and function, including dosage compensation [15,16] [18,36].HOX transcript antisense RNA (HOTAIR) is a lncRNA which has regulatory functions of transcription and are transcribed from the antisense strand of homeobox C gene locus in chromosome 12. HOTAIR recruits Polycomb Repressive Complex 2 (PRC2) and histone demethylase complex [LSD1 (lysine specific demethylase 1)/CoREST (Co-repressor of RE1-silencing transcription factor)/REST]; then leads to histone H3 tri-methylated at lysine 27 (H3K27me3) and histone H3 dimethyl Lys4 (H3K4me2); consequently results in gene silencing.…”

Induction of a novel isoform of the lncRNA HOTAIR in Claudin‐low breast cancer cells attached to extracellular matrix

“…The lncRNA genes exhibit tissue‐specific expression patterns and regulate expression of the genes that are pivotal to development and cancer (Cabili et al ., 2011; Guttman et al ., 2009). lncRNA can act as a recruiter and scaffold for assembly of chromatin modifiers on their target genes (Chu et al ., 2011; Gupta et al ., 2010; Spitale et al ., 2011; Tsai et al ., 2010; Wang and Chang, 2011). The lncRNA HOX transcript antisense RNA (HOTAIR) is elevated in breast cancer and promotes metastasis (Gupta et al ., 2010; Rinn et al ., 2007).…”