Advances and challenges towards the study of RNA-RNA interactions in a transcriptome-wide scale

Abstract

Background: RNA molecules play crucial roles in various biological processes. Their regulation and function are mediated by interacting with other molecules. Among them RNA-RNA interactions (RRIs) are important in many basic cellular activities including transcription, RNA processing, localization, and translation. However, we just start to unveil the complexity of the knowledge and underlying mechanisms of RRIs. Results: In this review, we will summarize approaches for RRI identifications, including both conventional, focused biophysical and biochemical methods and recently developed large scale sequencing-based techniques. We will also discuss discoveries per RRI type revealed by using these technologies, as well as challenges towards a systematic and functional understanding of RRIs. Conclusions: The development of sequencing-based techniques has revolutionized the study of RRIs. Applying these techniques in multiple organisms has identified thousands of RRIs, many of which could potentially regulate multiple aspects of gene expression. However, despite the great breakthrough, the RNA-RNA interactome of any species remains far from complete due to intrinsic complex nature of RRI and limitations in current techniques. More efficient experimental methods and computational framework are needed to obtain the full image of RRI networks, and their possible regulatory roles in biology and medicine.

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

“…Methods that allow the detection of RNA‐RNA interactions may also provide insight into RNA localization mechanisms. These include techniques which combine the use of cross‐linking agents, proximity ligation and RNA‐seq to profile RNA interactomes (CLASH, SPLASH, PARIS, LIGR‐seq and MARIO) 119 . Combining these techniques with RBP‐based approaches may have the potential to yield rich data sets that detail the RBP‐RNA and RNA‐RNA interactions that regulate RNA localization.…”

Experimental Approaches to Identify Host Factors Important for Influenza Virus

“…RNA:RNA interactions between virus and host, although not unusual in virology, are a relatively understudied category of interactions during influenza virus infection (Damas et al 2019). Tools are already available to study RNA:RNA interactions, and these have provided our first glimpse into how RNA:RNA interactions define influenza virus genome organization (Gong et al 2018;Dadonaite et al 2019). Extension of these techniques into host: virus interaction studies opens up entirely new areas of investigation.…”

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

“…The interaction between two RNAs (inter-molecular) or between different regions of the same RNA molecule (intra-molecular) are one of mechanisms of the regulatory action of ncRNAs. Since computational methods can provide just a prediction of RNA-RNA interaction (RRI), different low and high-throughput methods have been developed to directly solve these molecular events [91].…”