Adenovirus VA RNA-derived miRNAs target cellular genes involved in cell growth, gene expression and DNA repair

Adenovirus virus-associated (VA) RNAs are processed to functional viral miRNAs or mivaRNAs. mivaRNAs are important for virus production, suggesting that they may target cellular or viral genes that affect the virus cell cycle. To look for cellular targets of mivaRNAs, we first identified genes downr...

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Detalles Bibliográficos
Autores: Aparicio, O. (Óscar)|||/items/6cb4bb8d-b30b-4cde-aaec-5b2c411fb059, Carnero, E. (Elena)|||/items/0270d018-997a-4a86-a675-079b99a00528, Abad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954, Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d, Guruceaga-Martínez, E. (Elizabeth)|||/items/71d8df8b-4fab-4004-a38e-4057dddc85b2, Segura, V. (Víctor)|||/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4, Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23174
Acceso en línea:https://hdl.handle.net/10171/23174
Access Level:acceso abierto
Palabra clave:MicroRNAs/metabolism
RNA Interference
RNA, Viral/metabolism
Descripción
Sumario:Adenovirus virus-associated (VA) RNAs are processed to functional viral miRNAs or mivaRNAs. mivaRNAs are important for virus production, suggesting that they may target cellular or viral genes that affect the virus cell cycle. To look for cellular targets of mivaRNAs, we first identified genes downregulated in the presence of VA RNAs by microarray analysis. These genes were then screened for mivaRNA target sites using several bioinformatic tools. The combination of microarray analysis and bioinformatics allowed us to select the splicing and translation regulator TIA-1 as a putative mivaRNA target. We show that TIA-1 is downregulated at mRNA and protein levels in infected cells expressing functional mivaRNAs and in transfected cells that express mivaRNAI-138, one of the most abundant adenoviral miRNAs. Also, reporter assays show that TIA-1 is downregulated directly by mivaRNAI-138. To determine whether mivaRNAs could target other cellular genes we analyzed 50 additional putative targets. Thirty of them were downregulated in infected or transfected cells expressing mivaRNAs. Some of these genes are important for cell growth, transcription, RNA metabolism and DNA repair. We believe that a mivaRNA-mediated fine tune of the expression of some of these genes could be important in adenovirus cell cycle.