Evolution and coordination of gene expression through RNA-protein interactions
Abstract/Contents
- Abstract
- Reprogramming of a gene's expression pattern by acquisition or loss of sequences recognized by specific regulatory RNA binding proteins has the potential to be a major mechanism in the evolution of biological regulatory programs. Systematic study of orthologous Puf3 proteins across eukaryotes revealed that the RNA binding specificity is highly conserved, yet the identity and functional commonalities of their RNA targets have extensively diverged. We identified six eukaryotic lineages within which RNA targets of Puf3 orthologs have been conserved over 250-500 million years of evolution. Focusing on Puf proteins and their targets across 80 fungi, we were able to construct a parsimonious model for their evolutionary history. This history entails changes in the number of Puf genes, modifications in the RNA binding specificity of the Puf proteins, and extensive and coordinated changes in the Puf targets and, in one remarkable case, switching of hundreds of mRNA targets from Puf3 to Puf4. Binding of Puf3 to more than 200 RNAs whose protein products are predominantly involved in the production and organization of mitochondrial complexes pre-dates the origin of budding yeasts and filamentous fungi and was maintained throughout the evolution of budding yeast. In filamentous fungi, more than 150 of the ancestral Puf3 targets were gained en masse by Puf4, with one lineage maintaining both Puf3 and Puf4 as regulators and another lineage losing Puf3 as a regulator of these RNAs. Gene expression profiling and sequence analysis suggest that the regulatory consequences of Puf4 in filamentous fungi are distinct from that of Puf3 for this set of RNAs in budding yeast. In filamentous fungi, Puf4 broadened its target set to include mitochondrial genes involved in the tricarboxylic acid (TCA) cycle among other functions, and Puf3 targets in these fungi diversified, notably gaining interactions with the mRNAs encoding the electron transport chain (ETC) complex I. These and many other changes involving just this handful of Puf proteins in fungi strongly support their role in coordinating gene expression through "RNA operons" and indicate an extensive involvement of RNA binding proteins and their RNA targets in the adaptation and reprogramming of gene expression. The timing and nature of these changes are distinct from those observed at the level of transcriptional control, suggesting that RNA-protein interactions provide an additional and rich infrastructure from which gene expression can be reconfigured. Beyond the static pictures of extant gene expression programs of currently employed model organisms, identifying the changes in gene expression programs throughout evolution will provide a unique window into the make-up, logic, and malleability of gene expression, ultimately contributing to our understanding of and ability to engineer this program.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Hogan, Gregory John | |
|---|---|---|
| Associated with | Stanford University, Department of Biochemistry. | |
| Primary advisor | Brown, Patrick O'Reilly, 1954- | |
| Primary advisor | Herschlag, Daniel | |
| Thesis advisor | Brown, Patrick O'Reilly, 1954- | |
| Thesis advisor | Herschlag, Daniel | |
| Thesis advisor | Straight, Aaron, 1966- | |
| Thesis advisor | Yeh, Ellen | |
| Advisor | Straight, Aaron, 1966- | |
| Advisor | Yeh, Ellen |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Gregory John Hogan. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Gregory Hogan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...