Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
With improved methods to explore the transcriptome, in recent years there have been great advances in identifying and understanding non-coding RNAs. Regulatory pathways involving small RNAs, such as microRNAs, are now being elucidated in detail, and functions for long non-coding RNAs are also coming to light. The articles in this series discuss insights into the biology of non-coding RNAs of all sizes in a wide range of organisms.
Loci that encode long non-coding RNAs (lncRNAs) can be complex and function through multiple modalities. The authors provide a framework for elucidating the physiological roles of lncRNAs using genetically engineered mouse models, including whole-gene deletion, transcription termination, reporters and transgene rescue strategies.
PIWI-interacting RNAs (piRNAs) have numerous crucial biological roles, particularly transposon silencing in the germ line. In this Review, the authors describe our latest understanding of piRNA biogenesis and functions across diverse species, highlighting how, despite the universal importance of transposon control, different species have evolved intriguingly distinct mechanistic routes to achieve this.
Virtually all studies depend on annotations, maps of the genome that catalogue gene loci and the sequences of their transcripts. This Review discusses the state of currently available long non-coding RNA annotations and the impact of emerging technologies such as long-read sequencing.
MicroRNAs (miRNAs) have emerged as crucial components of gene-regulatory networks, in which they act alone or cooperatively to regulate gene expression. Here, the authors provide a systems-biological view of miRNA function and how disruption of miRNA networks can lead to malignancy.
Numerous long non-coding RNAs (lncRNAs) have emerged as having important and mechanistically diverse roles in gene regulation. However, for most lncRNAs, evolution is rapid and functions remain uncharacterized. This Review describes how comparative genomics and transcriptomics can provide broad insights into the functional importance and evolutionary trajectories of lncRNAs across species, and offers guidance for cross-species studies of lncRNAs.
The observation that many, if not all, functional enhancers generate non-coding enhancer RNAs (eRNAs) has raised critical questions regarding the potential biological roles of the enhancer transcription process and, indeed, of eRNAs. This article reviews fundamental insights into the inter-regulation of enhancers and promoters and discusses unresolved questions regarding the functional role of enhancers as transcription units in genome regulation.
Long non-coding RNAs (lncRNAs) are a class of RNAs with great molecular and regulatory diversity. This Review discusses how, beyond their lack of protein-coding potential, some types of lncRNAs are known to exhibit features that are distinct from mRNAs, including their transcriptional regulation, localization, processing, biological capabilities and degradation. Such properties underlie many of the key cellular functions of lncRNAs.
MicroRNAs (miRNAs) repress gene expression both through initiating mRNA degradation and through translational repression. This Review describes how molecular studies and structural data are revealing key insights into both mechanisms of miRNA-mediated gene repression in animals, including their intricate interplay, and are posing new questions for future research.
This Review describes our latest understanding of the range of functions of tRNAs. Emerging roles include the tight regulation of tRNA biogenesis to meet the translational needs of different cell types, cleavage and covalent modification of tRNAs in stress signalling, and diverse mechanistic links to various diseases.
Small and long non-coding RNAs have emerged as key regulators of gene expression through their direct and indirect actions on chromatin. This Review describes how RNAs form powerful surveillance systems that detect and silence inappropriate transcription events, and how such systems provide a memory of these events via self-reinforcing epigenetic loops.
The RNA World concept is the idea that billions of years ago — before current life based on DNA, RNA and proteins — the primary living substance was RNA or something chemically similar. This Review highlights the challenges and solutions of this point of view, particularly for the synthesis and replication of RNA, and how various types of molecular cooperation probably had important roles.
This Review discusses the main experimental approaches for microRNA (miRNA) target identification, as well as the modulators and the consequences of miRNA–target interactions. It also highlights the role of computational modelling in furthering the conceptual understanding of miRNA functions in gene regulatory networks.
Discoveries over the past decade portend a paradigm shift in molecular biology; evidence suggests that RNA is not only functional as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression. This Timeline article surveys the emergence of the previously unsuspected world of regulatory RNA from a historical perspective.
Our knowledge of the diverse types and roles of long non-coding RNAs (lncRNAs) is rapidly increasing. This Review discusses our latest understanding of lncRNAs that have validated functional roles in various differentiation and developmental processes.
Antisense transcription is increasingly being recognized as an important regulator of gene expression across all kingdoms of life and through a range of regulatory modes. Antisense transcripts are also emerging as facilitators of rapid evolution of gene regulation.
This Review discusses roles for microRNAs in adult animals — including in adult stem cells, metabolism and in cancer — and how functions in adults can be distinguished from developmental roles using a range of methods. Understanding adult-specific functions has implications for therapeutic manipulation of miRNAs.
PIWI-interacting RNAs (piRNAs) have important roles in various species, particularly in silencing transposons in the germ line. This Review describes our latest understanding of various steps in this process, from the specification of piRNA-producing loci to piRNA processing and nuclear effector functions, including a role in transgenerational epigenetic inheritance.
Argonaute proteins are vital components of small-RNA-guided modes of gene regulation. Recent studies have provided important details about classical modes of Argonaute function, such as their structure and loading with small RNAs, and have also revealed unexpected roles in other cellular functions.
In addition to well-known roles in the cytoplasm, a growing number of functions for small RNAs in the nucleus are being discovered. These include roles in transcriptional repression, epigenetic modifications and genome stability. This Review considers examples from animals, plants and fungi.
Owing to the important role of microRNAs in gene regulation, profiling repertoires of expressed microRNAs can be informative in basic research and clinical settings. This Review describes the methods that are available for microRNA profiling and considerations for choosing among analytical options.
MicroRNAs are key regulators of gene expression. Emerging evidence points towards a reciprocal relationship between microRNAs and their targets and for roles of non-target RNAs and proteins in this crosstalk.
The role of non-coding RNAs (ncRNAs) in disease is best understood for microRNAs in cancer. However, there is increasing interest in the disease-related roles of other ncRNAs — including piRNAs, snoRNAs, T-UCRs and lncRNAs — and in using this knowledge for therapy.
Our increasing understanding of microRNA biology, combined with sequence information from diverse animal genomes, has shed light on how microRNAs and their targets evolve and how the evolution of microRNA-containing regulatory networks has contributed to organismal complexity.
The ways in which an RNA molecule folds to form structures can be crucial to its function, and so methods for studying RNA structures make an important contribution to understanding transcriptomes. Experimental approaches in this field are being advanced by coupling them to high-throughput sequencing.
RNA interference can elicit specific gene silencing and so holds great potential for treating infectious or genetic diseases. Several small-RNA-based therapies have now reached clinical trials, but further work is still needed to improve delivery and efficacy.
The relative contribution of mRNA degradation and translational repression to gene regulation by plant and animal microRNAs has been controversial. This question, along with the molecular details of the two modes of regulation, has been addressed by several recent studies.
MicroRNAs and long non-coding RNAs regulate diverse aspects of animal embryogenesis. Recent evidence from several species shows their importance in driving and maintaining cell fate decisions, from early patterning through to tissue specification and morphogenesis.
To achieve their diverse regulatory functions, specific small RNA strands need to pair with the correct Argonaute protein partners. This Review discusses the recent substantial progress in understanding how small RNA sorting occurs in animals and plants.
MicroRNAs are post-transcriptional regulatory molecules that control many developmental and cellular processes. Recent studies have revealed that microRNAs themselves are subject to sophisticated control at various levels, including biogenesis, function and decay. Such regulation greatly contributes to the specific functions of microRNAs.
The CRISPR system uses small RNAs to provide bacteria and archaea with an adaptive defence mechanism against foreign nucleic acids. Recent studies have increased the understanding of mechanisms of CRISPR interference, its roles in microbial physiology and evolution and its potential applications.
Recent transcriptomic studies have revealed that diverse small RNAs are transcribed from the regions around gene promoters. This Review considers questions prompted by the discovery of these transcripts; for example, what is their origin and are they functional?
Alterations in microRNA function contribute to the pathogenesis of many cancers. Recent studies have shown that such changes can result not only from mutations but also from epigenetic silencing or the dysregulation of transcription factors that target specific microRNAs.
Constructs containing artificial microRNA target sites have the potential to improve a range of therapeutic strategies that are based on gene delivery or viruses. The same technology can be used for experimental purposes, in animal transgenics and to study the functions of microRNAs.
The recent discovery that most of the eukaryotic genome is transcribed has focused interest on the importance of non-coding transcripts. Long non-coding RNAs are emerging as a class with wide-ranging functions in gene regulation.
Small RNAs — including miRNAs, siRNAs and piRNAs — differ in their biogenesis, modes of target regulation and biological functions. There are also interconnections between these pathways, which compete and collaborate in some of their regulatory and protective roles.
