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Whole-genome sequencing efforts, primarily those by the ENCODE and FANTOM consortia, revolutionized our appreciation of the variety as well as the sheer number of genetic elements in the genome. A key finding that emerged from these efforts is that the majority of the genome is transcribed to produce ...

Whole-genome sequencing efforts, primarily those by the ENCODE and FANTOM consortia, revolutionized our appreciation of the variety as well as the sheer number of genetic elements in the genome. A key finding that emerged from these efforts is that the majority of the genome is transcribed to produce non-coding RNAs (i.e., RNAs that do not encode proteins). These are often >200 bp-long and thus loosely categorized as long non-coding RNAs (lncRNAs). While a handful of lncRNAs have been associated with a variety of biological processes, ranging from developmental cell fate decisions to human pathologies, most lncRNAs remain uncharacterized. As a result, there still remains a lot to be desired as regards molecular, physiological, and mechanistic roles of lncRNAs. Nevertheless, discoveries in lncRNA biology have allowed postulation of such concepts as:

1. lncRNAs being a central component in the epigenetic control of gene expression

2. Given the ability of RNA to act as a ‘molecular glue’ and the fact that most transcribed RNAs are non-coding, lncRNAs can be critical for the generation, integrity, and function of subcellular “phase-separated” condensates

3. Given that lncRNAs are mostly nuclear, rich in repeat elements, and able to interact with DNA, RNA, and proteins, they also play a role in genome organization both locally and globally

As the field is leaving its infancy, with this Research Topic, we aim at summarizing the current state of the art and discussing emerging directions as a collection of focused reviews, as well as original research and theory articles. Provocative yet constructive opinion pieces on lncRNA biology are also welcome.

Given the breadth of the field, this Research Topic will focus on addressing the following:

• lncRNAs as epigenetic controllers of gene expression in development, homeostasis, and disease.
• lncRNAs in phase separation, formation, and function of subcellular condensates, including nuclear condensates and stress granules.
• lncRNAs in 3D genome organization and gene regulation.
• Functional genomics and biochemical approaches to comprehensively dissect lncRNAs.
• Emerging technologies, including systems biology tools, to address RNA-DNA and RNA-protein interactions, RNA secondary and tertiary structures, RNA-dependent DNA conformation changes, RNA-dependent protein subcellular localization.

Keywords: lncRNAs, epigenetics, gene expression, nuclear condensates, stress granules, 3D genome organization, development, homeostasis, disease, systems biology


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