Dark Dimensions of the RNA Regulome (D2R2)

This solicitation invites participation in an Ideas Lab whose focus will be the exploration of novel approaches to elucidate the evolutionary and functional significance of RNA transcripts that do not encode proteins as well as the technological innovations that may arise from the ability to harness the power of non-coding RNA to solve pressing societal problems. Ideas Labs are intensive, facilitated workshops to find innovative solutions to grand challenge problems. The overarching aim of this Ideas Lab is to bring together a diverse set of researchers from multiple disciplines spanning biology, chemistry, physics, mathematics, computer and information sciences, and engineering, to stimulate generation and execution of innovative research that advances our understanding of the origin, diversity, and functions of non-coding RNAs. Outcomes from this Ideas lab should lead to new theories and models for understanding non-coding RNAs, new approaches to manipulate and control non-coding RNA activity, and biotechnological innovations based on the expected research results that spur the bioeconomy and enhance our ability to predict and mitigate the effects of changing environments on organisms and ecosystems.

Although our ability to sequence, analyze, and manipulate genomes has significantly advanced in the last two decades, we still have not solved the grand challenge of understanding how genomes produce phenotypic variation and give rise to taxonomic and functional diversity. Despite substantial investments and widespread implementation, genome-wide association studies have only succeeded in explaining a small fraction of the genetic variation in most organisms, and much of this variation maps onto poorly characterized non-protein-coding regions of genomes. Many of those ‘dark’ regions of the genome are transcribed into RNAs that do not encode proteins but may show signatures of evolutionary conservation, unusual structural features, and/or non-random expression patterns that are suggestive of their functional roles.

There has been a surge of interest in uncovering the cellular, physiological, and developmental roles of non-coding RNAs in recent years, and it is now clear that non-coding RNAs affect a wide range of cellular processes, including regulation of gene expression, developmental processes, metabolism, physiology, and even interactions with other organisms. Understanding the role of non-coding RNA in these cellular processes will be essential to enable the rational design of biological systems for biotechnology applications.  Nevertheless, the vast majority of non-coding RNAs remain uncharacterized, and our understanding of their functional roles remains in its infancy. It is likely that the underlying rules governing the evolution and function of non-coding RNAs are different from those of protein-coding ones; hence fresh perspectives and novel approaches are needed to unveil the syntax and semantics of this hidden language. A wealth of new biology awaits discovery, along with hitherto unimagined biotechnology innovations, powered by transformative technologies and approaches to illuminate the dark dimensions of the RNA regulome, and decipher the role of non-coding RNAs in shaping the form and function of living organisms through evolution.