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Reverse transcriptase encoded by a human transposable element.

S L Mathias1, A F Scott, H H Kazazian

  • 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Science (New York, N.Y.)
|December 30, 1991
PubMed
Summary
This summary is machine-generated.

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Researchers found that the human L1 element possesses reverse transcriptase activity, crucial for the spread of repetitive DNA sequences in mammals. This discovery sheds light on the mechanisms of retrotransposition and genome evolution.

Area of Science:

  • Molecular Biology
  • Genetics
  • Evolutionary Biology

Background:

  • L1 elements are abundant, repetitive DNA sequences in mammalian genomes.
  • Their structure suggests propagation via retrotransposition, a process requiring reverse transcriptase activity.

Purpose of the Study:

  • To investigate the reverse transcriptase activity of the human L1 element.
  • To confirm the enzymatic function of L1-encoded proteins.

Main Methods:

  • The second open reading frame of the human L1.2A element was expressed as a fusion protein in Saccharomyces cerevisiae.
  • The fusion protein was targeted to Ty1 virus-like particles.
  • Reverse transcriptase activity was assayed.
  • A specific missense mutation (Y/F-X-D-D motif) was introduced to assess its impact on activity.

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Main Results:

  • The expressed human L1 fusion protein demonstrated reverse transcriptase activity.
  • A missense mutation in the conserved Y/F-X-D-D motif abolished this activity.
  • This confirms the enzymatic capability of the L1-encoded protein.

Conclusions:

  • Human L1 elements encode a functional reverse transcriptase.
  • This enzyme is essential for the retrotransposition and proliferation of L1 elements.
  • L1 reverse transcriptase may be a source for the activity needed by other mammalian retroelements.