microRNAs (miRNAs) are short non-coding RNAs that down-regulate gene expression by pairing with sequences in the 3UTR of target mRNAs. They play critical roles in diverse developmental and physiological events but the exact function of most miRNAs remains to be elucidated. Identification of bona fide targets is challenging due to partial base pairing between miRNAs and target 3UTRs. To understand miRNA function during early vertebrate development, I first analyzed the general rules for miRNA:mRNA base pairing. By comparing the silencing ability of different miRNA recognition sites, I show that combinations of weak binding sites are just as effective as perfect sites for miRNA function. In addition, I uncovered a novel tissue-inductive role for miR-92 during early zebrafish development. Most previous work has focused on control of a number of cancer-related genes by miR-92, but here, using gain-of-function, loss-of-function, target identification, and genetic epistasis experiments, I demonstrate that miR-92 also regulates transcription factor gata5 and that such regulation is essential for proper endoderm formation and left-right patterning in zebrafish.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07092010-001651 |
| Date | 09 July 2010 |
| Creators | Li, Nan |
| Contributors | Ronald B Emeson, Joshua T Gamse, Todd R Graham, James G Patton, Lilianna Solnica-Krezel |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-07092010-001651/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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