As with scaffolds, RNA decoy interactions can be transient and regulatable. RNA can also function as a “decoy” molecule, which we define similarly to a scaffold, except that in this case, two or more macromolecules are brought together by the RNA decoy in a complex that prevents the sequestered macromolecules from forming other interactions and functional complexes at other cellular locations. Thus, RNAs can scaffold both stable cellular complexes and facilitate transient macromolecular interactions. While rRNAs, bound by ribosomal proteins, are generally regarded as mostly static ribonucleoprotein complexes (RNPs) ( Mathis et al., 2017)- although study of “specialized ribosomes” may shift this view ( Genuth and Barna, 2018) – lncRNA and mRNAs are generally thought to facilitate more transient, regulatable interactions. Beyond this, long non-coding RNAs (lncRNAs) and even messenger RNAs (mRNAs) are now increasingly being shown to perform a diverse array of scaffolding roles. By this definition, perhaps the most well-known RNA scaffold molecules are ribosomal RNAs (rRNAs), which provide the structural and catalytic core of ribosomes around which approximately 57–78 ribosomal proteins (depending on species) ( Lecompte et al., 2002) assemble to generate functioning ribosomes. These macromolecules may be proteins, other RNAs or DNA molecules that in the absence of the RNA scaffold do not interact or do so very poorly. In this review, we define an “RNA scaffold” as an RNA molecule capable of bringing together 2 or more macromolecules to form a complex with functional activity. Whereas proteins have long been appreciated to sometimes function as scaffolds, it is becoming increasingly clear that RNA molecules can also facilitate a wide range of interactions among and between proteins and nucleic acids, in many cellular contexts. One mechanism for this localization is the use of molecular scaffolds to enable particular interactions while inhibiting off-pathway interactions, thus increasing the efficiencies of the biological processes in which they are involved in Zappulla and Cech (2006). This necessitates ways to bring biomolecules together in a tightly regulated manner. 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. 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. 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. 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. 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. RNA molecules are increasingly being identified as facilitating or impeding the interaction of proteins and nucleic acids, serving as so-called scaffolds or decoys. ![]() Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, United States.
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