Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
RNA. 2011 Apr;17(4):665-74. doi: 10.1261/rna.2462011. Epub 2011 Jan 31.

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

Author information

  • 1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

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.

PMID:
21282347
[PubMed - indexed for MEDLINE]
PMCID:
PMC3062177
Free PMC Article

Images from this publication.See all images (5)Free text

FIGURE 1.
FIGURE 2.
FIGURE 3.
FIGURE 4.
FIGURE 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk