EGO-1, an essential Caenorhabditis elegans RNA-directed RNA polymerase, modulates gene expression through the messenger RNA-templated production of short antisense effector RNAs
Abstract/Contents
- Abstract
- The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. These genes must direct the regulation of cell proliferation, meiosis, and sex determination, as well as gamete formation and fertilization. Several genes required for small RNA biogenesis and function are also required for the proper organization and development of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for C. elegans germ-line development and efficient RNAi of germ-line expressed genes. Additionally, ego-1 mutants have been shown to exhibit defects in heterochromatin assembly on unpaired DNA and proper chromosome segregation during meiosis. Despite our understanding of the morphology of ego-1 mutant worms, it has remained unclear how the loss of a putative RdRP can cause such dramatic phenotypes in the C. elegans germline. That is, what role does EGO-1 play in promoting the development of the germline? There is strong evidence for the requirement of the C. elegans RdRP RRF-3 in producing endogenous small RNAs that target mRNA produced from specific genes. Additionally, there is evidence that EGO-1 may interact directly with chromatin. The questions become what target (or perhaps targets) is being disrupted in the ego-1 mutant and are they being disrupted at the chromatin or RNA level? Using high-throughput small RNA and messenger RNA sequencing we found that EGO-1 is required to produce small RNAs antisense to a number of germline-expressed genes through several developmental stages. We found that these genes fall into several classes including genes required for kinetochore (klp-7) and nuclear pore (npp-3) assembly, as well as the production of histone-modifying (set-21) and centromeric proteins (hcp-3). We also found several RNAi-related genes to be targets of EGO-1 (csr-1, mut-14, mut-16, prg-1, tsn-1). Finally, we show a strong correlation between the loss of small RNAs and the rise of mRNA levels in ego-1(-) animals.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Copyright date | 2011 |
| Publication date | 2010, c2011; 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Maniar, Jay Mahesh |
|---|---|
| Associated with | Stanford University, Department of Genetics |
| Primary advisor | Fire, Andrew Zachary |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Chen, Chang-Zheng |
| Thesis advisor | Pringle, John |
| Thesis advisor | Sarnow, P. (Peter) |
| Thesis advisor | Villeneuve, Anne, 1959- |
| Advisor | Chen, Chang-Zheng |
| Advisor | Pringle, John |
| Advisor | Sarnow, P. (Peter) |
| Advisor | Villeneuve, Anne, 1959- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jay Mahesh Maniar. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Jay Mahesh Maniar
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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