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Full-Text Articles in Life Sciences
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Natalie G. Farny
Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …
Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros
Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros
Victor R. Ambros
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 of 3,404 miRNA-associated mRNA transcripts was identified by immunoprecipitation of the RNA-induced silencing complex components AIN-1 and AIN-2. Our analysis of this AIN-IP dataset revealed enrichment for defining characteristics of functional miRNA-target interactions, including structural accessibility of target sequences, total free energy of miRNA-target hybridization and topology of base-pairing to the 5' seed region of the miRNA. We used these enriched characteristics as the basis for a quantitative miRNA target prediction method, …
Systematic Analysis Of Dynamic Mirna-Target Interactions During C. Elegans Development, Liang Zhang, Molly Hammell, Brian Kudlow, Victor Ambros, Min Han
Systematic Analysis Of Dynamic Mirna-Target Interactions During C. Elegans Development, Liang Zhang, Molly Hammell, Brian Kudlow, Victor Ambros, Min Han
Victor R. Ambros
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. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA family-mRNA pairs with temporally …
Immunopurification Of Ago1 Mirnps Selects For A Distinct Class Of Microrna Targets, Xin Hong, Molly Hammell, Victor Ambros, Stephen Cohen
Immunopurification Of Ago1 Mirnps Selects For A Distinct Class Of Microrna Targets, Xin Hong, Molly Hammell, Victor Ambros, Stephen Cohen
Victor R. Ambros
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 effective means to identify their targets. Combined efforts from computational prediction, miRNA over-expression or depletion, and biochemical purification have identified thousands of potential miRNA-target pairs in cells and organisms. Complementarity to the miRNA seed sequence appears to be a common principle in target recognition. Other features, including miRNA-target duplex stability, binding site accessibility, and local UTR structure might affect target recognition. Yet computational approaches using such contextual features have yielded largely …
Metabolite Sensing In Eukaryotic Mrna Biology, Carina Clingman, Sean Ryder
Metabolite Sensing In Eukaryotic Mrna Biology, Carina Clingman, Sean Ryder
Sean P. Ryder
All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second-messenger systems. More recent studies reveal that metabolites also affect post-transcriptional regulatory mechanisms. Here, we review the increasing number of connections between metabolism and post-transcriptional regulation in eukaryotic organisms. First, we present evidence that riboswitches, a common mechanism of metabolite sensing in bacteria, also function in eukaryotes. Next, we review an example of a double stranded RNA modifying enzyme that directly interacts with a metabolite, suggesting a link between RNA editing and metabolic state. Finally, …
A Quantitative Rna Code For Mrna Target Selection By The Germline Fate Determinant Gld-1, Jane Wright, Dimos Gaidatzis, Mathias Senften, Brian Farley, Eric Westhof, Sean Ryder, Rafal Ciosk
A Quantitative Rna Code For Mrna Target Selection By The Germline Fate Determinant Gld-1, Jane Wright, Dimos Gaidatzis, Mathias Senften, Brian Farley, Eric Westhof, Sean Ryder, Rafal Ciosk
Sean P. Ryder
RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is …
Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder
Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder
Sean P. Ryder
Myelin-associated glycoprotein (MAG) is a major component of myelin in the vertebrate central nervous system. MAG is present in the periaxonal region of the myelin structure, where it interacts with neuronal proteins to inhibit axon outgrowth and protect neurons from degeneration. Two alternatively spliced isoforms of Mag mRNA have been identified. The mRNA encoding the shorter isoform, known as S-MAG, contains a termination codon in exon 12, while the mRNA encoding the longer isoform, known as L-MAG, skips exon 12 and produces a protein with a longer C-terminal region. L-MAG is required in the central nervous system. How inclusion of …