Short RNAs show a long history

October 02, 2008

MicroRNAs, the tiny molecules that fine-tune gene expression, were first discovered in 1993. But it turns out they've been around for a billion years.

Evidence reported in Nature on October 1 by scientists in the lab of Whitehead Member and Howard Hughes Medical Institute investigator David Bartel provides a window into the early evolution of these key regulators, placing their origin within the earliest of animal lineages. The research also suggests that microRNAs present early on have undergone extensive changes, which likely have altered their functions across various lineages.

"This is the first evidence that microRNAs were present within the earliest animal lineages and are not just characteristic of more complex animals," says Andrew Grimson, a postdoctoral fellow in Bartel's lab. Scientists knew that microRNAs existed within bilaterians, an evolutionary group that includes everything from worms to fruit flies to humans, he explains. "Remarkably, we discovered their presence within sponge, a member of the earliest diverging group of animals."

The scientists used high-throughput sequencing to probe samples from animals that diverged before the origin of bilaterian animals. The sponge (Amphimedon queenslandica) represents a group of animals that split off in evolution very early, whereas the starlet sea anemone (Nematostella vectensis) split off more recently.

The sequences of microRNAs within each lineage were different from each other, suggesting that microRNA functions are almost certainly very different in these different lineages. "In a relatively narrow spectrum of evolution microRNAs are often conserved," says Grimson. "But in a broader spectrum they have completely changed. This suggests that microRNA evolution is more flexible and may be evolving more rapidly than suspected."

Researchers also pinpointed piRNAs, another class of small RNAs, among these two species. Although less is known about piRNAs, they characteristically have longer sequences than microRNAs and are thought to dampen the activity of transposons-chunks of DNA that can move around the genome, causing mutations.

"It appears that both microRNAs and piRNAs have been available to shape gene expression throughout the evolution of animals and perhaps even helped to usher in the era of multicellular animal life," says Bartel.

Whitehead Institute for Biomedical Research

MicroRNAs: From Basic Science to Disease Biology
by Krishnarao Appasani (Editor), Sidney Altman (Editor), Victor R. Ambros (Editor)

MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand...

Next-Generation MicroRNA Expression Profiling Technology: Methods and Protocols (Methods in Molecular Biology)
by Jian-Bing Fan (Editor)

The rapid pace of microRNA (miRNA) research continues to drive the advances of techniques for miRNA expression profiling, and innovative technologies that are more sensitive, specific, quantitative, and that are compatible with a wide range of biospecimens have been developed during the past few years. In Next-Generation MicroRNA Expression Profiling Technology: Methods and Protocols, expert researchers in the field contribute detailed examinations of the most current approaches being used today. This volume includes comprehensive coverage of methodologies that have been developed for miRNA profiling, as well as next-gen sequencing technology, miRNA databases, and specialized applications, such as cancer studies and miRNA-based non-invasive biomarker development. Written in the...

MicroRNAs and Cancer (Current Cancer Research)
by Carlo Croce (Editor)

The aim of this book is to reveal to a large spectrum of audience including biologists and physicians the extent of the microRNAs revolution in the cancer society. Alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancer: cancer initiation and progression can involve microRNAs (miRNAs) - small non-coding RNAs that can regulate gene expression. At the present time, the main mechanism of microRNAs alteration in cancer cells seems to be represented by aberrant gene expression, characterized by abnormal levels of expression for mature and/or precursor miRNA sequences in comparison with the corresponding normal tissues. Loss or amplification of miRNA genes has been reported in a variety of cancers and altered patterns of miRNA expression may...

MicroRNAs in Development: Methods and Protocols (Methods in Molecular Biology)
by Tamas Dalmay (Editor)

Since the discovery of microRNAs, developmental biologists have striven to understand the role of miRNAs in development and disease. MicroRNAs in Development: Methods and Protocols collects contributions from expert researchers in order to provide practical guidelines to this complex study. Divided into three convenient sections, this detailed volume covers various techniques to detect and profile miRNA expression, followed by protocols to manipulate the activity of miRNAs in various organisms, and it concludes with a section that outlines different methods to identify and validate miRNA targets in animals and plants. Written in the highly successful Methods in Molecular Biology™ series format, chapters contain introductions to their respective topics, lists of the necessary materials...

microRNAs in Development, Volume 99 (Current Topics in Developmental Biology)
by Eran Hornstein (Editor)

This new volume in the "Current topics in Developmental Biology" series concentrates on MicroRNAs in Development. It includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA. With an international team of authors, this volume is a must-have addition for researchers and students alike.Concentrates on MicroRNAs in Development. Includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA. With an international team of authors, this volume is a must-have addition for researchers and students alike.

MicroRNAs in Plant Development and Stress Responses (Signaling and Communication in Plants)
by Ramanjulu Sunkar (Editor)

Precise regulation of gene expression in both time and space is vital to plant growth, development and adaptation to biotic and abiotic stress conditions. This is achieved by multiple mechanisms, with perhaps the most important control being exerted at the level of transcription. However, with the recent discovery of microRNAs another ubiquitous mode of gene regulation that occurs at the post-transcriptional level has been identified. MicroRNAs can silence gene expression by targeting complementary or partially complementary mRNAs for degradation or translational inhibition. Recent studies have revealed that microRNAs play fundamental roles in plant growth and development, as well as in adaptation to biotic and abiotic stresses. This book highlights the roles of individual miRNAs that...

MicroRNA Protocols (Methods in Molecular Biology)
by Shao-Yao Ying (Editor)

MicroRNA Protocols provides diverse, novel, and useful descriptions of miRNAs in several species, including plants, worms, flies, fish, chicks, mice, and humans. These include some useful adaptations and applications that could be relevant to the wider research community who are already familiar with the identification of miRNAs. This volume will stimulate the reader to explore diverse ways to understanding the mechanism in which miRNAs facilitate the molecular aspects of the biomedical research.

MicroRNAs in Cancer Translational Research
by William C.S. Cho (Editor)

MicroRNA (miRNA) is a cutting-edge topic in the scientific and medical fields. This is a timely and specialized book focusing on the current understanding of miRNAs and the potential for their application in cancer diagnosis, prognosis, and therapeutic targets. It also provides discussion of the lessons learned from translational miRNA studies and exploration of the next steps required to advance this field. The unique book comprises 22 in-depth chapters by gathering unparalleled topics of interest in miRNAs by international team of world-renowned experts in the field. The first fifteen chapters provide comprehensive and expert perspectives on the most common cancers from bench to bedside applications, there is no current book structured in this cancer-oriented way. The next seven...

Plant MicroRNAs: Methods and Protocols (Methods in Molecular Biology)
by Blake C. Meyers (Editor), Pamela J. Green (Editor)

MicroRNAs constitute a particularly important class of small RNAs given their abundance, broad phylogenetic conservation and strong regulatory effects, with plant miRNAs uniquely divulging their ancient evolutionary origins and their strong post-transcriptional regulatory effects. In Plant MicroRNAs: Methods and Protocols, experts in the field present chapters that focus on the identification, validation, and characterization of the miRNA class of RNAs, and address important aspects about heterochromatic small interfering RNAs. In addition, the methods contained in this volume emphasize miRNA analyses, but also include ways to distinguish one class of small RNAs from another. As a volume in the highly successful Methods in Molecular Biology™ series, chapters include brief introductions...

MicroRNA Interference Technologies
by Zhiguo Wang (Author)

MicroRNAs (miRNAs), endogenous noncoding regulatory mRNAs of around 22-nucleotides long, have rapidly emerged as one of the key governors of the gene expression regulatory program in cells of varying species, with ever-increasing implications in the control of the fundamental biological processes and in the pathogenesis of adult humans. The exciting findings in this field have inspired us with a premise and a promise that miRNAs will ultimately be taken to the heart for therapy of human disease. While miRNAs have been considered potential therapeutic targets for disease treatment, it remains obscured what strategies we can use to achieve the goal. In the past years, we have witnessed a rapid evolving of many creative, innovative, inventive strategies and methodologies pertinent to miRNA...