Editorial: A Year in Review: Discussions in RNA

Sybille Krauß^1*Nicoletta Potenza^2*

• ¹University of Siegen, Siegen, Germany
• ²Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy

Over the last two decades, there has been a tremendous expansion in our understanding of RNA 13 biology. A plethora of novel RNA biotypes has been discovered, and it is now increasingly clear that 14 RNA molecules, beyond serving as a carrier of genetic information between DNA and proteins, play 15 pivotal roles in the control of gene expression, by adding multilayered regulatory complexity. In fact, 16 their structural diversity and complexity are reflected in great functional versatility, which makes them 17 capable of interacting with other RNA molecules, DNA, and proteins, thus regulating key biological 18 pathways, both in physiological and pathological contexts. 19This Research Topic aimed to stimulate discussions in the continuously evolving field of RNA 20 research, bringing together four articles offering novel research tools and mechanistic insights along 21 with translational opportunities contributing to scientific advances in RNA research. 22The study by Filcenkova et al. [1] addresses a common challenge in the field of RNA-protein 23 interaction, namely the lack of an easy-to-perform, rapid, and robust method to detect RNA-protein 24 binding. In their study the authors use the RNA-binding protein HuR (human antigen R) that binds to 25 its target mRNAs via an AU-rich element as an example to establish a novel read-out system. In this 26 system a split luciferase reporter is used. One luciferase fragment is expressed as a fusion protein with 27HuR. The second Streptavidin-coated luciferase fragment is coupled to a biotinylated RNA-oligo 28 comprising an AU-rich HuR-binding element. The binding between HuR and its target RNA-oligo 29 then leads to reconstitution of the functional luciferase that can be detected via luminescence. This 30 assay was then used to screen a set of small molecules targeting the HuR-RNA interaction, showing 31 that this novel read-out technique can be used for compounds screening. Since RNA-protein 32 interactions play an important regulatory role in several biological processes, this technique will be 33 useful not only for studying the HuR-RNA interaction, but can be used for many other studies. 34Besides the association of RNAs with their interacting proteins, the subcellular localization of RNA is 35 of utmost importance. RNA transcripts are not randomly distributed in the cell but localize to specific 36 subcellular compartments to fulfil their timely and locally regulated function.