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MicroRNAs grease the cell's circadian clockwork
June 01, 2009Most of our cells possess an internal clock, a group of genes displaying a cyclic expression pattern that reaches a peak once a day. A large number of circadian genes are expressed by organs such as the liver, whose activity needs to be precisely regulated over the course of the day. A team of researchers of the National Centre of Competence in Research Frontiers in Genetics, based at the University of Geneva, Switzerland, reveals that an important regulator of this molecular oscillator is a specific microRNA. The latter belongs to a class of small RNA molecules that regulate the production of proteins in our cells. Thus far, little was known about their function within the circadian clockwork. The study by Ueli Schibler's team, published in the 1st June edition of Genes & Development, fills in this important gap.
Living beings have adapted to the alternation between night and day by developing an internal clock, located in the brain. It allows synchronising gene expression and physiological functions with geophysical time. In addition, most of our body's cells possess their own subsidiary oscillators, a group of genes displaying a cyclic expression pattern that reaches a peak every twenty-four hours.
More than 350 genes involved in metabolism, including that of cholesterol and lipids, are expressed in liver cells in a cyclic fashion. Many of them are also influenced by rhythmic food intake. Their activity must therefore be fine-tuned and synchronised with precision to ensure cohesion between diverse metabolic processes.
MicroRNAs induce gene silencing
Ueli Schibler, from the Molecular Biology Department of the University of Geneva, focuses on the mechanisms controlling the tiny oscillators in liver cells. MicroRNAs were among the potential factors likely to be involved in clock gene regulation. The common property of these small molecules lies in their ability to inhibit the synthesis of specific proteins, thus allowing cells to reduce the activity of certain genes at a given time.
"We have studied the role of a microRNA called miR-122, which is highly abundant in liver. It has caught considerable attention for its role in regulating cholesterol and lipid metabolism and in aiding the replication of hepatitis C virus" explains David Gatfield, one of Professor Schibler's collaborators.
Performance of the molecular oscillator-
The researchers' team has discovered that miR-122 is tightly embedded in the output system of the circadian clock in hepatocytes. This microRNA regulates numerous circadian genes, impinging on the amplitude and duration of their expression. Conversely, the synthesis of miR-122 involves a transcription factor that is otherwise known for its function in the circadian clock.
-and viral replication
"It will be exciting to investigate whether the connection between circadian rhythms and miR-122 also extends to this microRNA's role in hepatitis C virus replication", points out David Gatfield. Knowing whether viral multiplication is gated to specific times of the day would contribute significantly to our understanding of the life cycle of this formidable pathogen.
Scientists have uncovered over the past years the role of microRNAs in crucial physiological functions such as growth and programmed cell death, as well as carcinogenesis. Ueli Schibler's team adds a stone to this edifice by placing miR-122 within the clock gene machinery.
Cold Spring Harbor Laboratory
MicroRNAs induce gene silencing
Ueli Schibler, from the Molecular Biology Department of the University of Geneva, focuses on the mechanisms controlling the tiny oscillators in liver cells. MicroRNAs were among the potential factors likely to be involved in clock gene regulation. The common property of these small molecules lies in their ability to inhibit the synthesis of specific proteins, thus allowing cells to reduce the activity of certain genes at a given time.
"We have studied the role of a microRNA called miR-122, which is highly abundant in liver. It has caught considerable attention for its role in regulating cholesterol and lipid metabolism and in aiding the replication of hepatitis C virus" explains David Gatfield, one of Professor Schibler's collaborators.
Performance of the molecular oscillator-
The researchers' team has discovered that miR-122 is tightly embedded in the output system of the circadian clock in hepatocytes. This microRNA regulates numerous circadian genes, impinging on the amplitude and duration of their expression. Conversely, the synthesis of miR-122 involves a transcription factor that is otherwise known for its function in the circadian clock.
-and viral replication
"It will be exciting to investigate whether the connection between circadian rhythms and miR-122 also extends to this microRNA's role in hepatitis C virus replication", points out David Gatfield. Knowing whether viral multiplication is gated to specific times of the day would contribute significantly to our understanding of the life cycle of this formidable pathogen.
Scientists have uncovered over the past years the role of microRNAs in crucial physiological functions such as growth and programmed cell death, as well as carcinogenesis. Ueli Schibler's team adds a stone to this edifice by placing miR-122 within the clock gene machinery.
Cold Spring Harbor Laboratory
MicroRNAs Current Events and MicroRNAs News RSSExperimental agent reduces breast cancer metastasis to bone
Researchers have reduced breast cancer metastasis to bone using an experimental agent to inhibit ROCK, a protein that was found to be over-expressed in metastatic breast cancer.
MicroRNA-mediated metastasis suppression
Metastases are responsible for over 90% of cancer deaths. In the upcoming issue of G&D, Dr. Robert Weinberg (MIT) and colleagues lend molecular insight into how microRNAs suppress tumor metastasis.
Texas A&M researchers find new mechanism for circadian rhythm
Molecules that may hold the key to new ways to fight cancer and other diseases have been found to play an important role in regulating circadian rhythm, says Liheng Shi, a researcher in Texas A&M's Department of Veterinary Integrative Biosciences.
UCSF scientists illuminate how microRNAs drive tumor progression
UCSF researchers have identified collections of tiny molecules known as microRNAs that affect distinct processes critical for the progression of cancer.
Lung cancer suppresses miR-200 to invade and spread
Primary lung cancer shifts to metastatic disease by suppressing a family of small molecules that normally locks the tumor in a noninvasive state, researchers at The University of Texas M. D. Anderson Cancer Center report in the Sept. 15 edition of Genes and Development.
Scientists Use MicroRNAs to Track Evolutionary History for First Time
The large group of segmented worms known as annelids, which includes earthworms, leeches and bristle worms, evolved millions of years ago and can be found in every corner of the world.
MicroRNAs circulating in blood show promise as biomarkers to detect pancreatic cancer
A blood test for small molecules abnormally expressed in pancreatic cancer may be a promising route to early detection of the disease.
Predicting cancer prognosis
Researchers led by Dr. Soheil Dadras at the Stanford University Medical Center have developed a novel methodology to extract microRNAs from cancer tissues.
MicroRNA in human saliva may help diagnose oral cancer
Researchers continue to add to the diagnostic alphabet of saliva by identifying the presence of at least 50 microRNAs that could aid in the detection of oral cancer, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Dental researchers confirm microRNAs as biomarkers for oral cancer detection
A new study published by researchers at the UCLA School of Dentistry substantiates the effectiveness of measuring the microRNAs present in saliva to detect oral squamous cell carcinoma.
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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... |
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microRNA: Biology, Function & Expression (Nuts & Bolts series) by Neil J. Clarke; Philippe Sanseau (Author) Providing a comprehensive overview of a fast-emerging field, this volume dedicated to the biological role of microRNAs (miRNAs) discusses methods for identifying and characterizing their functions and looks at potential applications of microRNA research in medicine and pharmacology. miRNAs are small, noncoding RNA molecules that appear to regulate gene expression. Found in plant and animal species and possibly traceable back to ancient forms of life, miRNAs are now estimated to regulate a third or more of genes in the human genome. The Editors have included material from some of the very best, most active and upcoming researchers in the field, to provide the reader with a rounded overview of the biology, function and expression of miRNAs. The chapters are grouped according to the... |
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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... |
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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. |
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Microrna Profiling in Cancer: A Bioinformatics Prospective by Yuriy Gusev (Editor) The recent discovery of microRNAs - a new class of non-coding RNAs - has revolutionized modern biomedical sciences. This book presents current advances in the emerging interdisciplinary field of microRNA research of human cancers from a unique perspective of quantitative sciences: bioinformatics, computational and systems biology and mathematical modeling. This volume contains adaptations and critical reviews of the recent state-of-the-art studies, ranging from technological advances in microRNA detection and profiling, clinically oriented microRNA profiling in several human cancers, to a systems biology analysis of global patterns of microRNA regulation of signaling and metabolic pathways. Interactions with transcription factor regulatory networks and mathematical modeling of miRNA... |
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Current Perspectives in microRNAs (miRNA) by Shao-Yao Ying (Editor) Nearly 97 percent of the human genome is the non-coding DNA, which varies from one species to another, and changes in these sequences are frequently noticed to manifest clinical and circumstantial malfunction. Numerous non-protein-coding genes are recently found to encode microRNAs, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. MicroRNAs (miRNAs), small single-stranded 17-25 nucleotide RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Currently over 1000 native miRNA species found in vertebrates and many more new miRNA homologs continue to be identified; however, most... |
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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... | |
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MicroRNA Methods, Volume 427 (Methods in Enzymology) by John J. Rossi (Editor) MicroRNAs (miRNA) are tiny bits of genetic material that were unknown nearly 10 years ago but now represent an exciting field of study in biology. Upon their discovery, researchers revealed for the first time a new mechanism by which microRNA can stop the function of messenger RNA (mRNA) by literally cutting it in half, interfering with the normal function of specific messenger RNAs in gene expression. This "expression" of genes that code for essential proteins is essentially what controls whether a cell turns into a liver, lung, or brain cell, for example. Understanding what activates this process - or stops it - is a key to understanding the biological process and builds a foundation for advances in medicine and other fields. This volume in Methods in Enzymology presents... |
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Micrornas in Development and Cancer by Frank J Slack (Editor) MicroRNAs have recently emerged as key regulators of gene expression during development and are frequently misexpressed in human disease states, in particular cancer. These 22-nucleotide-long transcripts act to promote or repress cell proliferation, migration and apoptosis during development, all of which are processes that go awry in cancer. Thus, microRNAs have the ability to behave like oncogenes or tumor suppressors. In addition, their small size and molecular properties make them amenable as targets and therapeutics in cancer treatment. This book goes into detail on how microRNAs represent a paradigm shift in thinking about gene regulation during development and disease, and provide the oncologist with a potentially powerful new battery of agents to diagnose and treat cancer. | |
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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... |
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