Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 9 of 9

Full-Text Articles in Life Sciences

Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder Oct 2015

Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder

Sean P. Ryder

Maternally supplied mRNAs encode proteins that pattern early embryos in many species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo transition, and early embryogenesis. To understand how these RNA-binding proteins contribute to development, it is necessary to determine how they select specific mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for oocyte maturation--an essential part of meiosis that prepares oocytes for fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate that …


A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder Sep 2015

A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder

Sean P. Ryder

Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside …


Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder Sep 2015

Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder

Sean P. Ryder

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA …


A Compendium Of Caenorhabditis Elegans Rna Binding Proteins Predicts Extensive Regulation At Multiple Levels, Alex Tamburino, Sean Ryder, Albertha Walhout May 2015

A Compendium Of Caenorhabditis Elegans Rna Binding Proteins Predicts Extensive Regulation At Multiple Levels, Alex Tamburino, Sean Ryder, Albertha Walhout

Sean P. Ryder

Gene expression is regulated at multiple levels, including transcription and translation, as well as mRNA and protein stability. Although systems-level functions of transcription factors and microRNAs are rapidly being characterized, few studies have focused on the posttranscriptional gene regulation by RNA binding proteins (RBPs). RBPs are important to many aspects of gene regulation. Thus, it is essential to know which genes encode RBPs, which RBPs regulate which gene(s), and how RBP genes are themselves regulated. Here we provide a comprehensive compendium of RBPs from the nematode Caenorhabditis elegans (wRBP1.0). We predict that as many as 887 (4.4%) of C. elegans …


Metabolite Sensing In Eukaryotic Mrna Biology, Carina Clingman, Sean Ryder May 2015

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 May 2015

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 …


Quaking Regulates Hnrnpa1 Expression Through Its 3' Utr In Oligodendrocyte Precursor Cells, Nancy Zearfoss, Carina Clingman, Brian Farley, Lisa Mccoig, Sean Ryder May 2015

Quaking Regulates Hnrnpa1 Expression Through Its 3' Utr In Oligodendrocyte Precursor Cells, Nancy Zearfoss, Carina Clingman, Brian Farley, Lisa Mccoig, Sean Ryder

Sean P. Ryder

In mice, Quaking (Qk) is required for myelin formation; in humans, it has been associated with psychiatric disease. QK regulates the stability, subcellular localization, and alternative splicing of several myelin-related transcripts, yet little is known about how QK governs these activities. Here, we show that QK enhances Hnrnpa1 mRNA stability by binding a conserved 3' UTR sequence with high affinity and specificity. A single nucleotide mutation in the binding site eliminates QK-dependent regulation, as does reduction of QK by RNAi. Analysis of exon expression across the transcriptome reveals that QK and hnRNP A1 regulate an overlapping subset of transcripts. Thus, …


Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder May 2015

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 …


Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk May 2015

Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk

Sean P. Ryder

Although the decision between stem cell self-renewal and differentiation has been linked to cell-cycle modifications, our understanding of cell-cycle regulation in stem cells is very limited. Here, we report that FBF/Pumilio, a conserved RNA-binding protein, promotes self-renewal of germline stem cells by repressing CKI-2(Cip/Kip), a Cyclin E/Cdk2 inhibitor. We have previously shown that repression of CYE-1 (Cyclin E) by another RNA-binding protein, GLD-1/Quaking, promotes germ cell differentiation. Together, these findings suggest that a post-transcriptional regulatory circuit involving FBF and GLD-1 controls the self-renewal versus differentiation decision in the germline by promoting high CYE-1/CDK-2 activity in stem cells, and inhibiting CYE-1/CDK-2 …