Publications New

The sequence and roles in developmental progression of the microRNA let-7 are conserved. In general, transcription of the let-7 primary transcript (pri-let-7) occurs early in development, whereas proc...

C. elegans heterochronic genes determine the timing of expression of specific cell fates in particular stages of developing larva. However, their broader roles in coordinating developmental events acr...

MicroRNAs are small, noncoding RNAs that regulate gene expression at the post-transcriptional level in essentially all aspects of Caenorhabditis elegans biology. More than 140 genes that encode microR...

Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidate...

MicroRNAs (miRNAs) are small noncoding RNA molecules that function in RNA silencing and posttranscriptional regulation of gene expression. miRNAs in biofluids are being used for clinical diagnosis as ...

The double-stranded RNA-binding protein Staufen has been implicated in various post-transcriptional gene regulatory processes. Here we demonstrate that the Caenorhabditis elegans homolog of Staufen, S...

MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific...

Biological robustness, the ability of an organism to maintain a steady-state output as genetic or environmental inputs change, is critical for proper development. MicroRNAs have been implicated in bio...

Circulating miRNAs can be found in extracellular vesicles (EV) and could be involved in intercellular communication. Here, we report the biodistribution of EV associated miR-155 using miR-155 KO mouse...

Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). ...

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess th...

The preparation and high-throughput sequencing of cDNA libraries from samples of small RNA is a powerful tool to quantify known small RNAs (such as microRNAs) and to discover novel RNA species. Intere...

Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is kn...

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRN...

MicroRNAs guide many aspects of development in all metazoan species. Frequently, microRNAs are expressed during a specific developmental stage to perform a temporally defined function. The C. elegans ...

Background: Atrial fibrillation (AF) is the most common dysrhythmia in the U.S. and Europe. Few biomarkers exist to identify individuals at risk for AF. Cardiac microRNAs (miRNAs) have been implicated...

microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (A...

BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although mo...

Interview with Victor Ambros, who studies how microRNAs impact development.

In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of me...

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterio...

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regu...

Introduction: Novel methods of identifying individuals at risk for atrial fibrillation (AF) are needed. MicroRNAs (MiRNAs) regulate gene expression in a number of cardiovascular diseases, including AF...

Comment on: Transcoronary concentration gradients of circulating microRNAs. [Circulation. 2011]

MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nema...

Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key po...

Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environment...

Why do many microRNA gene mutants display no evident phenotype? Multiply mutant worms that are selectively impaired in genetic regulatory network activities have been used to uncover previously unknow...

BACKGROUND: Antisense reagents can serve as efficient and versatile tools for studying gene function by inhibiting nucleic acids in vivo. Antisense reagents have particular utility for the experimenta...

Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis e...

Comment on: The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell-cycle quiescence during C. elegans development. Buck SH, et al. Cell Cycle...

microRNAs comprise a few percent of animal genes and have been recognized as important regulators of a diverse range of biological processes. Understanding the biological functions of miRNAs requires ...

Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. ...

TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA...

The Caenorhabditis elegans genome encodes more than 100 microRNAs (miRNAs). Genetic analyses of miRNA deletion mutants have only provided limited insights into miRNA function. To gain insight into the...

Our appreciation of the significance of microRNAs to biology at large continues to be an evolving process.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally via antisense base-pairing. Although miRNAs are involved in a variety of important biological functions...

MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks ...

Target prediction for animal microRNAs (miRNAs) has been hindered by the small number of verified targets available to evaluate the accuracy of predicted miRNA-target interactions. Recently, a dataset...

The Drosophila let-7-Complex (let-7-C) is a polycistronic locus encoding three ancient microRNAs: let-7, miR-100, and fly lin-4 (miR-125). We find that the let-7-C locus is principally expressed in th...

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations ...

Small RNAs play crucial roles in regulation of gene expression in many eukaryotes. Here, we report the cloning and characterization of 18-26 nt RNAs in the social amoeba Dictyostelium discoideum. This...

A recent Keystone Symposium on 'MicroRNAs and siRNAs: Biological Functions and Mechanisms' was organized by David Bartel and Shiv Grewal (and was held in conjunction with 'RNAi for Target Validation a...

MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression b...

MicroRNAs are small noncoding RNAs that function by regulating target gene expression posttranscriptionally. They play a critical role in developmental and physiologic processes and are implicated in ...

C. elegans contains numerous small RNAs of ~21-24 nt in length. The microRNAs (miRNAs) are small noncoding RNAs produced by DCR-1- and ALG-dependent processing of self-complementary hairpin transcript...

A temporal gradient of the novel nuclear protein LIN-14 specifies the timing and sequence of stage-specific developmental events in Caenorhabditis elegans. The profound effects of lin-14 mutations on ...

Comment on: LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. [Science. 2005]

We have identified a DNA methyltransferase of the Dnmt2 family in Dictyostelium that was denominated DnmA. Expression of the dnmA gene is downregulated during the developmental cycle. Overall DNA meth...

Although hundreds of evolutionarily conserved microRNAs have been discovered, the functions of most remain unknown. Here, we describe the embryonic spatiotemporal expression profile, transcriptional r...

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. W...

MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conse...

The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which ...

Background The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans, lin-4 and ...

Comment on: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. [Cell. 1993]

MicroRNAs (miRNAs) and other small RNAs can be identified by cloning and sequencing cDNAs prepared from the ∼22-nt fraction of total RNA. Methods are described for the construction of cDNA libraries f...

Small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), are key components of an evolutionarily conserved system of RNA-based gene regulation in eukaryotes. They are involved in ...

lin-4 and let-7 are founding members of an extensive family of genes that produce small transcripts, termed microRNAs (miRNAs). In Caenorhabditis elegans, lin-4 and let-7 control the timing of postemb...

Drosophila geneticists have uncovered roles for microRNAs in the coordination of cell proliferation and cell death during development, and in stress resistance and fat metabolism. In C. elegans, a hom...

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that are processed from hairpin precursor transcripts by Dicer. miRNAs probably inhibit translation of mRNAs via imprecise antisense base-pairi...

MicroRNAs (miRNAs) are small noncoding RNA gene products about 22 nt long that are processed by Dicer from precursors with a characteristic hairpin secondary structure. Guidelines are presented for th...

In Caenorhabditis elegans, the heterochronic pathway controls the timing of developmental events during the larval stages. A component of this pathway, the let-7 small regulatory RNA, is expressed at ...

Animal genomes contain an abundance of small genes that produce regulatory RNAs of about 22 nucleotides in length. These microRNAs are diverse in sequence and expression patterns, and are evolutionari...

The lin-4 and let-7 antisense RNAs are temporal regulators that control the timing of developmental events in Caenorhabditis elegans by inhibiting translation of target mRNAs. let-7 RNA is conserved a...

Comment on: A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. [Science. 2001]

The nematode Caenorhabditis elegans develops through two major phases: the first phase, embryogenesis, consists of a rapid series of cleavage cell divisions leading to morphogenesis of a first stage l...

Studies of the nematode Caenorhabditis elegans have identified genetic and molecular mechanisms controlling temporal patterns of developmental events. Mutations in genes of the C. elegans heterochroni...

Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval f...

During postembryonic development of Caenorhabditis elegans, the heterochronic gene lin-14 controls the timing of developmental events in diverse cell types. Three alternative lin-14 transcripts are pr...

lin-4 encodes a small RNA that is complementary to sequences in the 3' untranslated region (UTR) of lin-14 mRNA and that acts to developmentally repress the accumulation of LIN-14 protein. This repres...

The lin-4 gene encodes a small RNA that is required to translationally repress lin-14 toward the end of the first larval stage of Caenorhabditis elegans development. To determine if the timing of LIN-...

In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1 degrees ) fate in response to a Ras-me...

C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression. The expression patt...

Mutations in the heterochronic gene lin-28 of C. elegans cause precocious development where diverse events specific to the second larval stage are skipped. lin-28 encodes a cytoplasmic protein with a ...

This chapter focuses on our current understanding of the C. elegans heterochronic gene pathway as determined by genetic characterization of the regulatory interactions among the genes (Ambros and Horv...

In Caenorhabditis elegans, the fates of the multipotent vulval precursor cells (VPCs) are specified by intercellular signals. The VPCs divide in the third larval stage (L3) of the wild type, producing...

Heterochronic genes control the timing of vulval development in the C. elegans hermaphrodite. lin-14 or lin-28 loss-of-function mutations cause the vulval precursor cells (VPCs) to enter S phase and t...

In Caenorhabditis elegans, the terminal differentiation of the hypodermal cells occurs at the larval-to-adult molt, and is characterized in part by the formation of a morphologically distinct adult cu...

A hierarchy of heterochronic genes, lin-4, lin-14, lin-28 and lin-29, temporally restricts terminal differentiation of Caenorhabditis elegans hypodermal seam cells to the final molt. This terminal dif...

The heterochronic genes of Caenorhabditis elegans encode part of a regulatory system that controls the temporal component of cell fates in development. The genes have been characterized genetically an...

lin-4 is essential for the normal temporal control of diverse postembryonic developmental events in C. elegans. lin-4 acts by negatively regulating the level of LIN-14 protein, creating a temporal dec...

We describe a dominant behavioral marker, rol-6(su-1006), and an efficient microinjection procedure which facilitate the recovery of Caenorhabditis elegans transformants. We use these tools to study t...

Beginning of article: In certain multicellular organisms, genetic regulatory systems that specify the timing of cell division, differentiation and morpho-genesis must accommodate environmental and phy...

The lin-29 gene product of C.elegans activates a temporal developmental switch for hypodermal cells. Loss-of-function lin-29 mutations result in worms that fail to execute a stage-specific pattern of ...

We report that a stage-specific developmental program, dauer larva formation, is temporally regulated by four heterochronic genes, lin-4, lin-14, lin-28, and lin-29. The effects of mutations in these ...

Independent reversions of mutations affecting three different Caenorhabditis elegans genes have each yielded representatives of the same set of extragenic suppressors. Mutations at any one of six loci...

The heterochronic genes lin-4, lin-14, lin-28, and lin-29 control the timing of specific postembryonic developmental events in C. elegans. The experiments described here examine how these four genes i...

We describe a general strategy for the genetic mapping in parallel of multiple restriction fragment length polymorphism (RFLP) loci. This approach allows the systematic identification for cloning of p...

The lin-14 locus of Caenorhabditis elegans plays an important role in specifying the normal timing and sequence of developmental events in the lateral hypodermal cell lineages. The results of gene dos...

Mutations in the Caenorhabditis elegans genes lin-14, lin-28, and lin-29 cause heterochronic developmental defects: the timing of specific developmental events in several tissues is altered relative t...

Using a rapid phenol extraction assay, an enzyme was purified from uninfected HeLa cells that can cleave the 5'-terminal protein (VPg) from poliovirus RNA. Both cytoplasmic and nuclear extracts had en...

The 5' terminal protein (VPg) on poliovirion RNA can be removed by cell-free extracts from a variety of uninfected cells. This soluble enzymatic activity is found in both nuclear and cytoplasmic extra...

Purification and partial characterization of the poliovirus RNA-linked protein (VPg) are described. VPg has been freed from the RNA by ribonuclease digestion and phenol extraction. Gel filtration chro...

A protein similar to that previously demonstrated on poliovirus RNA and replicative intermediate RNA (VPg) was found on all sizes of nascent viral RNA molecules and on the polyuridylic acid isolated f...

Intracellular poliovirus-specific RNA species can be measured directly by electrophoresis of total cytoplasmic nucleic acids through 1% agarose gels, resulting in the separation of single- and double-...

The 5'-terminus of poliovirus polyribosomal RNA is pUp. A candidate for the 5'-terminus of poliovirion RNA was recovered as a compound migrating toward the cathode when 32P-labeled virion RNA was comp...

Confluent chick embryo fibroblasts infected with the Ts68 mutant of Rous sarcoma virus were examined by scanning electron microscopy at the permissive (36 degrees) and nonpermissive (41 degrees) tempe...

In the frog (Rana pipiens) using a modification of the Fink-Heimer degeneration stain, a projection was traced from the lateral anterior thalamus via the lateral forebrain bundle to the ipsilateral st...