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Score: 1.00
Title: Regulation of cyclin T1 and HIV-1 Replication by microRNAs in resting CD4+ T lymphocytes .
Author: Chiang K Sung TL Rice AP
Journal: J Virol Citation: V : 86 P : 3244-52 Year: 2012 Type: MEDLINE
Literature: oryza Field: abstract Doc ID: pub22205749 Accession (PMID): 22205749
Abstract: The replication of integrated human immunodeficiency virus type 1 ( HIV-1 ) is dependent on the cellular cofactor cyclin T1 , which binds the viral Tat protein and activates the RNA polymerase II transcription of the integrated provirus . The activation of resting CD4 ( + ) T cells upregulates cyclin T1 protein levels independently of an increase in cyclin T1 mRNA levels , suggesting a translational repression of cyclin T1 in resting CD4 ( + ) T cells . Hypothesizing that microRNAs ( miRNAs ) repress cyclin T1 translation in resting CD4 ( + ) T cells and that this inhibition is lifted upon cell activation , we used microarray expression analysis to identify miRNAs miR-27b , miR-29b , miR-150 , and miR-223 as being significantly downregulated upon CD4 ( + ) T cell activation . The overexpression of these miRNAs decreased endogenous cyclin T1 protein levels , while treatment with the corresponding antagomiRs increased cyclin T1 protein levels . An miR-27b binding site within the cyclin T1 3 untranslated region ( 3UTR ) was identified and confirmed to be functional after the mutation of key resides abrogated the ability of miR-27b to decrease the expression of a luciferase reporter upstream of the cyclin T1 3UTR . Ago2 immunoprecipitation revealed an association with cyclin T1 mRNA that was decreased following treatment with miR-27b and miR-29b antagomiRs . Cells overexpressing miR-27b showed decreased viral gene expression levels of the HIV-1 reporter virus and a decreased replication of strain NL4 . 3 ; a partial rescue of viral transcription could be seen following the transfection of cyclin T1 . These results implicate miR-27b as a novel regulator of cyclin T1 protein levels and HIV-1 replication , while miR-29b , miR-223 , and miR-150 may regulate cyclin T1 indirectly .
Matching Sentences: [ Sen. 6, subscore: 1.00 ]: Ago2 immunoprecipitation revealed an association with cyclin T1 mRNA that was decreased following treatment with miR-27b and miR-29b antagomiRs .
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