Mosquitoes are vectors of multiple viral pathogens, a large number of which are RNA viruses. Strategies for viral control may target the vector itself or the interaction between the virus and the vector. This application is based upon the hypothesis that RNA viruses have evolved specific mechanisms for evading the mRNA turnover machineries of the mosquito cell and therefore mRNA decay factors may represent a novel target for therapeutics. Our current knowledge of mRNA decay in insects is minimal thus the primary goals of this proposal must be to elucidate the factors and pathways involved in mRNA turnover in the Aedes mosquito and characterize their regulation. Using an in vitro approach that we have successfully adapted to mosquito cell extracts along with in vivo assays, the goal of Aim I is to characterize the processes of mRNA deadenylation, decapping and decay in mosquitoes.
In Aim II we will use this knowledge to gain insights into mechanisms of regulated mRNA decay mediated by togavirus 3' untranslated regions that we have observed.
The final aim of the application will address the underlying mechanisms responsible for how non- polyadenylated viral RNAs avoid degradation upon entry into the mosquito cell. In summary, this information will provide fundamental insights into insect molecular biology and virus-host interactions that will provide the groundwork for novel avenues of arbovirus control. ? ? ?
|Barnhart, Michael D; Moon, Stephanie L; Emch, Alexander W et al. (2013) Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus. Cell Rep 5:909-17|
|Moon, Stephanie L; Anderson, John R; Kumagai, Yutaro et al. (2012) A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA 18:2029-40|
|Dickson, Alexa M; Anderson, John R; Barnhart, Michael D et al. (2012) Dephosphorylation of HuR protein during alphavirus infection is associated with HuR relocalization to the cytoplasm. J Biol Chem 287:36229-38|
|Dickson, Alexa M; Wilusz, Jeffrey (2011) Strategies for viral RNA stability: live long and prosper. Trends Genet 27:286-93|
|Brackney, Doug E; Scott, Jaclyn C; Sagawa, Fumihiko et al. (2010) C6/36 Aedes albopictus cells have a dysfunctional antiviral RNA interference response. PLoS Negl Trop Dis 4:e856|
|Sokoloski, Kevin J; Dickson, Alexa M; Chaskey, Emily L et al. (2010) Sindbis virus usurps the cellular HuR protein to stabilize its transcripts and promote productive infections in mammalian and mosquito cells. Cell Host Microbe 8:196-207|
|Sokoloski, Kevin J; Chaskey, Emily L; Wilusz, Jeffrey (2009) Virus-mediated mRNA decay by hyperadenylation. Genome Biol 10:234|
|Sanchez-Vargas, Irma; Scott, Jaclyn C; Poole-Smith, B Katherine et al. (2009) Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway. PLoS Pathog 5:e1000299|
|Garneau, Nicole L; Wilusz, Carol J; Wilusz, Jeffrey (2008) Chapter 5. In vivo analysis of the decay of transcripts generated by cytoplasmic RNA viruses. Methods Enzymol 449:97-123|
|Sokoloski, Kevin; Anderson, John R; Wilusz, Jeffrey (2008) Development of an in vitro mRNA decay system in insect cells. Methods Mol Biol 419:277-88|
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