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Antisense Transcription in Gammaretroviruses as a Mechanism of Insertional Activation of Host Genes

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— 1 min read

Scientists at Aarhus University in Denmark have reported the identification of transcripts of negative polarity in simple murine leukemia virus (MLV), a novel mechanism of insertional activation of host genes. This discovery could have significant implications for the design of therapeutic vectors and our understanding of pervasive eukaryotic transcription. The researchers found that antisense transcription initiated in the U3 region of the proviral 5' long terminal repeat (LTR) and continued into cellular proto-oncogenes, creating chimeric transcripts consisting of viral and host sequence.

Key Takeaways:

  • Scientists at Aarhus University, Denmark, have identified transcripts of negative polarity in simple murine leukemia virus (MLV).
  • Antisense transcription initiated in the U3 region of the proviral 5' long terminal repeat (LTR) and continued into cellular proto-oncogenes, creating chimeric transcripts.
  • The phenomenon was validated in vivo using a knock-in mouse model homozygous for a single LTR at a position known to activate Nras in B-cell lymphomas.
  • A 5' rapid amplification of cDNA ends (RACE) analysis indicated a broad spectrum of initiation sites within the U3 region of the 5' LTR.
  • The study suggests a novel mechanism of insertional activation of host genes.
  • Elucidation of the nature and potential regulatory role of 5' LTR antisense transcription may be relevant to the design of therapeutic vectors.
  • The findings may contribute to the increasing recognition of pervasive eukaryotic transcription.

Statistics:

  • The study was published in the Journal of Virology (Volume 84, Issue 8, 2010).
  • The researchers analyzed 5' rapid amplification of cDNA ends (RACE) data, indicating initiation sites within the U3 region of the 5' LTR (3780-8).
  • The study involved a knock-in mouse model homozygous for a single LTR at a position known to activate Nras in B-cell lymphomas.
  • Antisense transcription initiated in the U3 region of the proviral 5' long terminal repeat (LTR) was observed in both T-cell and B-cell lymphomas induced by SL3-3 and Akv MLV.

Sources:

  • "Antisense transcription in gammaretroviruses as a mechanism of insertional activation of host genes. Journal of Virology, 2010;84(8):3780-8"
  • "For additional information, contact M.H. Rasmussen, CF Mollers Alle 3, Dept. of Molecular Biology, 1130, Aarhus University, DK-8000 Arhus C, Denmark"

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