Life Sciences Commons^™

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.

Caenorhabditis Elegans Micrornas Of The Let-7 Family Act In Innate Immune Response Circuits And Confer Robust Developmental Timing Against Pathogen Stress, Zhiji Ren, Victor R. Ambros

Victor R. Ambros

Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting …

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 …

Investigating The Role Of Wolbachia Endosymbionts In The Expansion Of The F Element In Drosophila Ananassae, Elizabeth J. Chen

Undergraduate Theses—Unrestricted

At 4.2 Mb overall, the Drosophila melanogaster Muller F element (dot chromosome) is an unusual autosome; it is broadly heterochromatic, but the distal 1.3 Mb has a gene density and expression pattern similar to other autosomes. More intriguing is the large expansion of the D. ananassae F element (~20 Mb). Elucidating the factors that contribute to this expansion could improve our understanding of how heterochromatic domains are maintained and amplified.

Previous analyses show that the lateral gene transfer (LGT) of Wolbachia (the most widespread intracellular bacteria in the Rickettsiales order) into the D. ananassae genome is an important contributor to …

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 …

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …