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This Focus on noncoding RNAs presents specially commissioned Commentaries, Reviews and a Perspective that highlight the remarkable functional diversity of these molecules and discuss recent advances and challenges in noncoding RNA biology. Cover design by Erin Dewalt. pp 1–36
The long-held view that the primary role of RNA is to code for proteins has been severely undermined. This Focus explores the remarkable functional diversity of RNA in light of recent breakthroughs in noncoding-RNA biology.
Cellular fate is determined by transcriptional networks and epigenetic states. In addition to protein factors, noncoding RNAs (ncRNAs), particularly microRNAs and long ncRNAs, are able to remodel transcriptional circuits and reshape epigenetic landscapes. This Commentary highlights the emerging roles of these ncRNAs in cellular reprogramming, transdifferentiation and organ regeneration.
Recent advances in RNA-sequencing technologies have led to the discovery of thousands of previously unannotated noncoding transcripts, including many long noncoding RNAs (lncRNAs) whose functions remain largely unknown. Here, the authors discuss considerations and best practices when identifying and annotating lncRNAs that should aid their functional and mechanistic exploration.
The natural versatility of RNA makes it an ideal substrate for bioengineering. Its structural properties and predictable base-pairing permit its use as molecular scaffold, and its ability to interact with nucleic acids, proteins and small molecules confers a regulatory potential that can be harvested to design RNA regulators in diverse contexts.
The ribosome is a complex molecular machine that is central to protein synthesis. This Review highlights the various roles of noncoding RNAs during the different steps of ribosome biogenesis and discusses the consequences for ribosome function.
RNA interference (RNAi) is a process by which small noncoding RNAs direct molecular machinery to silence gene expression. In this Review, Ipsaro and Joshua-Tor discuss the mechanisms and structures that govern RNAi in higher organisms.
In this Perspective, Spitale, Chang and Chu discuss recent technological advances that will aid in the functional characterization of long noncoding RNAs, which up to now has posed a substantial challenge.
All RAF kinase domain structures reported to date have adopted a dimer configuration. Marc Therrien, Frank Sicheri and colleagues now report a crystal structure of the BRAF monomeric 'off' state, providing insight into its catalytic activation.
5-Formylcytosine (5fC) is implicated in active DNA demethylation and has been proposed to act as an epigenetic signal. Balasubramanian and colleagues now report that this base modification imparts a unique, previously undescribed conformation to DNA.
Bacterial LPS O-antigen is synthesized with a narrow size range by polymerase WbdA and terminating protein WbdD. An extended coiled-coil domain in WbdD determines the length of the synthesized O-chain, acting as a molecular ruler.
Bacterial ABC importer GlnPQ has two fused substrate-binding domains (SBDs). Single-molecule FRET is now used to probe the conformational dynamics of the SBDs, which are shown to directly influence transport rates.
Different catalytic steps of endonuclease I-DmoI are captured crystallographically to allow direct observation of the generation of a DNA double-strand break. A third metal ion enters the active site and has a key role in hydrolysis.
Cytoplasmic dynein has multiple ATPase subunits, with AAA1 as the primary ATPase. Single-molecule and biochemical approaches reveal that AAA3 ATPase has a role in switching dynein between cargo-transport and microtubule-anchoring modes.
Myo1c is a monomeric, unconventional myosin that can sense mechanical force in the cell. The structure of Myo1c's entire tail and neck domains in complex with apocalmodulin reveals a new mode of calmodulin interaction.
Gronemeyer and colleagues identify naturally occurring double-stranded RNAs arising from sense-antisense transcript pairs and demonstrate that one of these RNAs, nds-2a, interacts with mitotic protein complexes and is required for cellular mitosis.
Noncoding RNAs are remarkably versatile molecules that accomplish a wide range of biological functions. This Focus highlights the roles of noncoding RNAs in biological processes ranging from translation to cellular reprogramming and reviews recent insights into the molecular mechanisms of different RNA-interference pathways. It also explores the potential of noncoding RNAs in synthetic biology and discusses challenges in the annotation and functional characterization of lncRNAs.
