Altered CELF1 binding to target transcripts in malignant T cells.

The RNA-binding protein, CELF1, binds to a regulatory sequence known as the GU-rich element (GRE) and controls a network of mRNA transcripts that regulate cellular activation, proliferation, and apoptosis. We performed immunoprecipitation using an anti-CELF1 antibody, followed by identification of copurified transcripts using microarrays. We found that CELF1 is bound to a distinct set of target transcripts in the H9 and Jurkat malignant T-cell lines, compared with primary human T cells.

Regulation of CUG-binding protein 1 (CUGBP1) binding to target transcripts upon T cell activation.

The RNA-binding protein, CUG-binding protein 1 (CUGBP1), regulates gene expression at the levels of alternative splicing, mRNA degradation, and translation. We used RNA immunoprecipitation followed by microarray analysis to identify the cytoplasmic mRNA targets of CUGBP1 in resting and activated primary human T cells and found that CUGBP1 targets were highly enriched for the presence of GU-rich elements (GREs) in their 3'-untranslated regions. The number of CUGBP1 target transcripts decreased dramatically following T cell activation as a result of activation-dependent phosphorylation of CUGBP1 and decreased ability of CUGBP1 to bind to GRE-containing RNA.

Global assessment of GU-rich regulatory content and function in the human transcriptome.

Unlike AU-rich elements (AREs) that are largely present in the 3'UTRs of many unstable mammalian mRNAs, the function and abundance of GU-rich elements (GREs) are poorly understood. We performed a genome-wide analysis and found that at least 5% of human genes contain GREs in their 3'UTRs with functional over-representation in genes involved in transcription, nucleic acid metabolism, developmental processes, and neurogenesis. GREs have similar sequence clustering patterns with AREs such as overlapping GUUUG pentamers and enrichment in 3'UTRs.

Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

Objective: HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression.

Methods: In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/μL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.