Long Noncoding RNAs, Chromatin, and Development

Abstract

The way in which the genome of a multicellular organism can orchestrate the differentiation of trillions of cells and many organs, all from a single fertilized egg, is the subject of intense study. Different cell types can be defined by the networks of genes they express. This differential expression is regulated at the epigenetic level by chromatin modifications, such as DNA and histone methylation, which interact with structural and enzymatic proteins, resulting in the activation or silencing of any given gene. While detailed mechanisms are emerging on the role of different chromatin modifications and how these functions are effected at the molecular level, it is still unclear how their deposition across the epigenomic landscape is regulated in different cells. A raft of recent evidence is accumulating that implicates long noncoding RNAs (lncRNAs) in these processes. Most genomes studied to date undergo widespread transcription, the majority of which is not translated into proteins. In this review, we will describe recent work suggesting that lncRNAs are more than transcriptional "noise", but instead play a functional role by acting as tethers and guides to bind proteins responsible for modifying chromatin and mediating their deposition at specific genomic locations. We suggest that lncRNAs are at the heart of developmental regulation, determining the epigenetic status and transcriptional network in any given cell type, and that they provide a means to integrate external differentiation cues with dynamic nuclear responses through the regulation of a metastable epigenome. Better characterization of the lncRNA-protein "interactome" may eventually lead to a new molecular toolkit, allowing researchers and clinicians to modulate the genome at the epigenetic level to treat conditions such as cancer.

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

“…These lncRNAs play important roles in tumor progression 18. LncRNAs have been confirmed to play a key role in gene epigenetic regulation, genome imprinting, X chromosome inactivation, and whole‐genome rearrangement 19, 20, 21. To the best of our knowledge, few differentially expressed lncRNAs have been reported to be associated with the tumorigenesis and progression of NPC.…”

Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases

“…Their expression is frequently linked to human cancer and other diseases (Panzitt et al 2007;Taft et al 2009). Some ncRNAs have critical functions in development (Caley et al 2010) and in the derivation of pluripotent stem cells (Loewer et al 2010). With this gene silencing approach suitable also for the generation of ncRNA-deficient cells, we provide a method that will help to unravel the cellular and molecular functions of these noncoding transcripts.…”

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

“…Previous studies have focused on the regulatory roles of lncRNAs in several biological processes, such as chromosome inactivation, genomic imprinting and development (5)(6)(7). Recently, increasing reports have revealed that lncRNAs are frequently dysregulated in various human cancers, including bladder cancer (8,9).…”