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Full-Text Articles in Genetics and Genomics
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Victor R. Ambros
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 anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …
The Evolution Of Our Thinking About Micrornas, Victor Ambros
The Evolution Of Our Thinking About Micrornas, Victor Ambros
Victor R. Ambros
Our appreciation of the significance of microRNAs to biology at large continues to be an evolving process.
Micrornas And Developmental Timing, Victor Ambros
Micrornas And Developmental Timing, Victor Ambros
Victor R. Ambros
MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode Caenorhabditis elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell fate choices and transitions between pluripotency and differentiation, microRNAs help to orchestrate developmental events throughout the developing animal, and to play tissue homeostasis roles important for disease, including cancer.
Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros
Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros
Victor R. Ambros
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 regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period …
Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros
Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros
Victor R. Ambros
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 unknown functions for numerous Caenorhabditis elegans microRNAs.
The Regulation Of Genes And Genomes By Small Rnas., Victor Ambros, Xuemei Chen
The Regulation Of Genes And Genomes By Small Rnas., Victor Ambros, Xuemei Chen
Victor R. Ambros
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 and as a Therapeutic', organized by Stephen Friend and John Maraganore). The 'MicroRNAs and siRNAs' meeting brought together scientists working on diverse biological aspects of small regulatory RNAs, including microRNAs, small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs and rasiRNAs). Among the themes discussed were the diversity of small regulatory RNAs and their developmental functions, their biogenesis, the identification of their regulatory targets, their mechanisms of action, and their roles …
Potent Effect Of Target Structure On Microrna Function, Peter Williams, Dang Long, Rosalind Lee, Chi Chan, Victor Ambros, Ye Ding
Potent Effect Of Target Structure On Microrna Function, Peter Williams, Dang Long, Rosalind Lee, Chi Chan, Victor Ambros, Ye Ding
Victor R. Ambros
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 by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for …
Characterization Of Microrna Expression Levels And Their Biological Correlates In Human Cancer Cell Lines., Caifu Chen, Arti Gaur, David Jewell, Yu Liang, Dana Ridzon, Jason Moore, Victor Ambros, Mark Israel
Characterization Of Microrna Expression Levels And Their Biological Correlates In Human Cancer Cell Lines., Caifu Chen, Arti Gaur, David Jewell, Yu Liang, Dana Ridzon, Jason Moore, Victor Ambros, Mark Israel
Victor R. Ambros
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 the pathogenesis of several human diseases including cancer. We examined the expression profiles of 241 human microRNAs in normal tissues and the NCI-60 panel of human tumor-derived cell lines. To quantify microRNA expression, we employed a highly sensitive technique that uses stem-loop primers for reverse transcription followed by real-time PCR. Most microRNAs were expressed at lower levels in tumor-derived cell lines compared with the corresponding normal tissue. Agglomerative hierarchical clustering analysis of microRNA …
Developmental Biology. Encountering Micrornas In Cell Fate Signaling., Xantha Karp, Victor Ambros
Developmental Biology. Encountering Micrornas In Cell Fate Signaling., Xantha Karp, Victor Ambros
Victor R. Ambros
Comment on: LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. [Science. 2005]
The Functions Of Animal Micrornas., Victor Ambros
The Functions Of Animal Micrornas., Victor Ambros
Victor R. Ambros
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 conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
A Short History Of A Short Rna, Victor Ambros, Rosalind Lee, Rhonda Feinbaum
A Short History Of A Short Rna, Victor Ambros, Rosalind Lee, Rhonda Feinbaum
Victor R. Ambros
Comment on: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. [Cell. 1993]
Identification Of Micrornas And Other Tiny Noncoding Rnas By Cdna Cloning, Victor Ambros, Rosalind Lee
Identification Of Micrornas And Other Tiny Noncoding Rnas By Cdna Cloning, Victor Ambros, Rosalind Lee
Victor R. Ambros
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 from small noncoding RNAs through the use of T4 RNA ligase, reverse transcriptase, and polymerase chain reaction. cDNAs are cloned in λ or plasmid vectors, and the sequences are compared to annotated genomic sequence databases, and analyzed by RNA folding programs to distinguish miRNA sequences from other small RNAs of similar size. Northern blot hybridization is used to confirm the expression of small RNAs in vivo.
Role Of Micrornas In Plant And Animal Development, Victor Ambros, James Carrington
Role Of Micrornas In Plant And Animal Development, Victor Ambros, James Carrington
Victor R. Ambros
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 many molecular interactions, including defense against viruses and regulation of gene expression during development. miRNAs interfere with expression of messenger RNAs encoding factors that control developmental timing, stem cell maintenance, and other developmental and physiological processes in plants and animals. miRNAs are negative regulators that function as specificity determinants, or guides, within complexes that inhibit protein synthesis (animals) or promote degradation (plants) of mRNA targets.
Microrna Pathways In Flies And Worms: Growth, Death, Fat, Stress, And Timing, Victor Ambros
Microrna Pathways In Flies And Worms: Growth, Death, Fat, Stress, And Timing, Victor Ambros
Victor R. Ambros
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 homolog of the well-known fly developmental regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway controlling developmental timing.
Micrornas And Other Tiny Endogenous Rnas In C. Elegans, Victor Ambros, Rosalind Lee, Ann Lavanway, Peter Williams, David Jewell
Micrornas And Other Tiny Endogenous Rnas In C. Elegans, Victor Ambros, Rosalind Lee, Ann Lavanway, Peter Williams, David Jewell
Victor R. Ambros
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-pairing. Small interfering RNAs (siRNAs) are similar in size to miRNAs, but they recognize targets by precise complementarity and elicit RNA-mediated interference (RNAi). We employed cDNA sequencing and comparative genomics to identify additional C. elegans small RNAs with properties similar to miRNAs and siRNAs. RESULTS: We found three broad classes of small RNAs in C. elegans: (1) 21 new miRNA genes (we estimate that C. elegans contains approximately 100 distinct miRNA genes, about 30% of …
Micrornas: Tiny Regulators With Great Potential, Victor Ambros
Micrornas: Tiny Regulators With Great Potential, Victor Ambros
Victor R. Ambros
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 evolutionarily widespread, suggesting that they may participate in a wide range of genetic regulatory pathways.