Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.

Journal Article

Tat specific factor 1 (Tat-SF1) interacts with components of both the transcription and splicing machineries and has been classified as a transcription-splicing factor. Although its function as an HIV-1 dependency factor has been investigated, relatively little is known about the cellular functions of Tat-SF1. To identify target genes of Tat-SF1, we utilized a combination of RNAi and exon-specific microarrays. These arrays, which survey genome-wide changes in transcript and individual exon levels, revealed 450 genes with transcript level changes upon Tat-SF1 depletion. Strikingly, 98% of these target genes were down-regulated upon depletion, indicating that Tat-SF1 generally activates gene expression. We also identified 89 genes that showed differential exon level changes after Tat-SF1 depletion. The 89 genes showed evidence of many different types of alternative exon use consistent with the regulation of transcription initiation sites and RNA processing. Minimal overlap between genes with transcript-level and exon-level changes suggests that Tat-SF1 does not functionally couple transcription and splicing. Biological processes significantly enriched with transcript- and exon-level targets include the cell cycle and nucleic acid metabolism; the insulin signaling pathway was enriched with Tat-SF1 transcript-level targets but not exon-level targets. Additionally, a hexamer, ATGCCG, was over-represented in the promoter region of genes showing changes in transcription initiation upon Tat-SF1 depletion. This may represent a novel motif that Tat-SF1 recognizes during transcription. Together, these findings suggest that Tat-SF1 functions independently in transcription and splicing of cellular genes.

Full Text

Duke Authors

Cited Authors

  • Miller, HB; Robinson, TJ; Gordân, R; Hartemink, AJ; Garcia-Blanco, MA

Published Date

  • April 2011

Published In

Volume / Issue

  • 17 / 4

Start / End Page

  • 665 - 674

PubMed ID

  • 21282347

Electronic International Standard Serial Number (EISSN)

  • 1469-9001

Digital Object Identifier (DOI)

  • 10.1261/rna.2462011

Language

  • eng

Conference Location

  • United States