Gene regulation by sense–antisense overlap of polyadenylation signals

  1. Rui Gu,1,
  2. Zuo Zhang,2,
  3. Joshua N. DeCerbo and
  4. Gordon G. Carmichael
  1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut 06030-3301, USA

    Abstract

    We show here that expression of genes from convergent transcription units can be regulated by the formation of double-stranded RNA (dsRNA) in the region of overlapping polyadenylation signals. The model system employed is the mouse polyomavirus. The early and late genes of polyomavirus are transcribed from opposite strands of the circular viral genome. At early times after infection, the early genes are expressed predominantly. Late gene expression increases dramatically upon the onset of DNA replication, when a major defect in polyadenylation of the late primary transcripts generates multigenomic RNAs that are precursors to the mature late mRNAs. Embedded in these late pre-mRNAs are sequences complementary to the early RNAs that act to down-regulate early gene expression via A-to-I editing of dsRNAs. In this system, the defective polyadenylation, and consequently the production of multigenomic late RNAs, depends on the context, and perhaps also, on the A-to-I editing of the poly(A) signal that overlaps the 3′-end of early transcripts.

    Keywords

    Footnotes

    • 1 Present addresses: Division of Infectious Disease, Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA;

    • 2 Genetically Engineered Models Department, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065-0512, USA.

    • Reprint requests to: Gordon G. Carmichael, Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301, USA; e-mail: carmichael{at}nso2.uchc.edu; fax: (860) 679-8345.

    • Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1608909.

      • Received February 18, 2009.
      • Accepted March 26, 2009.

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