Abstract
RNA molecules are increasingly being identified as facilitating or impeding the interaction of proteins and nucleic acids, serving as so-called scaffolds or decoys. Long non-coding RNAs have been commonly implicated in such roles, particularly in the regulation of nuclear processes including chromosome topology, regulation of chromatin state and gene transcription, and assembly of nuclear biomolecular condensates such as paraspeckles. Recently, an increased awareness of cytoplasmic RNA scaffolds and decoys has begun to emerge, including the identification of non-coding regions of mRNAs that can also function in a scaffold-like manner to regulate interactions of nascently translated proteins. Collectively, cytoplasmic RNA scaffolds and decoys are now implicated in processes such as mRNA translation, decay, protein localization, protein degradation and assembly of cytoplasmic biomolecular condensates such as P-bodies. Here, we review examples of RNA scaffolds and decoys in both the nucleus and cytoplasm, illustrating common themes, the suitability of RNA to such roles, and future challenges in identifying and better understanding RNA scaffolding and decoy functions.
Highlights
The cell, with its variety of cellular compartments, varying polarities, competing interactions, and differing sites of molecular synthesis poses challenges to the formation of biomolecular interactions essential to all biological processes
Most known RNA scaffolds and decoys are defined as long non-coding RNAs (lncRNAs), which are a heterogenous group of RNAs > 200 nucleotides in length, and which generally lack long conserved open reading frames, though some may encode short peptides (Slavoff et al, 2013). lncRNAs are transcribed from diverse genomic locations including intergenic regions, and from within protein-coding gene elements including introns, exons, promoters, 5 and 3 untranslated regions (UTRs); both sense and antisense lncRNA transcription, with respect to the protein coding gene is observed (Khandelwal et al, 2015)
A decoy function of paraspeckles and nuclear-enriched abundant transcript 1 (NEAT1) is sequestration, and limiting export of messenger RNAs (mRNAs) harboring inverted repeat Alu elements in their 3 untranslated region (UTR; Alu elements are transposable elements that account for 11% of the human genome, and which likely derive from 7SL ncRNA (Deininger, 2011); discussed later)
Summary
The cell, with its variety of cellular compartments, varying polarities, competing interactions, and differing sites of molecular synthesis poses challenges to the formation of biomolecular interactions essential to all biological processes. The rest of this review will focus on flexible RNA scaffolds, which nucleate RNPs that lack a rigid structure In this case, the primary role of the RNA is typically to maintain spatial proximity of macromolecular components, and aid interactions that are often (though not always) more transient in nature. The primary role of the RNA is typically to maintain spatial proximity of macromolecular components, and aid interactions that are often (though not always) more transient in nature Such RNAs often lack strong sequence conservation and can tolerate large deletions or insertions, but remain functional (Zappulla and Cech, 2006). Certain structures or subdomains within the flexible RNA scaffold can be of critical functional importance; these can often be transferred in a modular-like fashion to other regions of the RNA and retain functional activity (Stuckenholz et al, 2003; Zappulla et al, 2005; Zappulla and Cech, 2006)
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