Squint, the arabidopsis ortholog of cyclophilin40, affects RNA silencing / Michael R. Smith.

Smith, Michael R.
xi, 122 p. : color ill. ; 29 cm.
Local subjects:
Penn dissertations -- Biology.
Biology -- Penn dissertations.
SQUINT (SQN) is the Cyclophilin40 ortholog in Arabidopsis thaliana . Loss-of-function mutations in this gene accelerate vegetative phase change, although the role of SQN in this developmental process is not understood. Recently, a number of genes involved in small RNA biogenesis have been shown to affect vegetative phase change due to their regulation of the miRNAs miR156, miR390 and the ta-siRNA, TAS3. sqn interacts more strongly with genes involved in miRNA biogenesis than with those involved in the ta-siRNA pathway. The strongest interaction was seen with ago1. Double mutants of sqn and weak alleles of ago1 resemble ago1 null mutants, suggesting that there is a functional connection between these two proteins. Further supporting this conclusion, we identified two sqn -like ago1 alleles (ago1-45, ago1-46); ago1-45 is remarkably similar to sqn both morphologically and molecularly. sqn and ago1-45 greatly affect the expression of some miRNAs and miRNA-targeted genes, while having only a small effect on the expression of some ta-siRNA-targeted genes. Furthermore, sqn and ago1-45 genetically interact strongly with genes involved in the miRNA pathway as opposed to genes involved in the ta-siRNA pathway.
Overexpressing miR156a suppresses many of the phase change aspects of sqn, suggesting that the upregulation of miR156-targeted SPLs is responsible for the majority of sqn's phenotype. In support of this, sqn was found to block the activity of miR156. Furthermore, loss of function mutations in spl2, spl9 and spl15 are epistatic to sqn. The other phenotypes seen in sqn are caused by the upregulation of miR164-targeted CUC2 and most likely a reduction in PNH function. In other organisms, CyP40 has been shown to interact with Hsp90. A mutation in hsp90.2 affects the expression of some miRNAs and interacts synergistically with sqn and ago1--45, implying that Hsp90.2 is also involved in RNA silencing. We hypothesize that SQN regulates the ability of a miRNA to enter RISC or its ability to stably bind to AGO1, by directly or indirectly affecting AGO1.
Adviser: R. Scott Poethig.
Thesis (Ph.D. in Biology) -- University of Pennsylvania, 2008.
Includes bibliographical references.
Local notes:
University Microfilms order no.: 3346191
Poethig, R. Scott, advisor.
University of Pennsylvania.
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