The scientists already knew that at one end of an L1 is a sequence that initiates transcription and at the other is a sequence that terminates transcription. Closer analysis, however, revealed that the L1s use a terminating sequence that is both unusual and somewhat weak, leading to so-called readthrough, meaning that transcription at times continues past what would ordinarily have been the stop point to the next downstream termination sequence.
To better understand this readthrough phenomenon, the scientists engineered an L1 with its marker sequence outside the L1, beyond the naturally occurring termination signal. And then beyond the marker itself, they placed a well-understood and highly efficient stop signal sequence, so that the gene products of any readthrough events could be easily identified because they would end with this marker. With the stronger downstream signal in place, the engineered L1s readily picked up neighboring DNA for retrotransposition.
"Overall, we found that, not only can these retrotransposons jump into genes, but readthrough events that pick up flanking DNA are not uncommon," Moran says.
In addition to Kazazian and Moran, the third author on the paper is graduate student Ralph J. DeBerardinis. While at Penn, Moran was supported by a Damon Runyon postdoctoral fellowship. Primary funding for the study was provided by the National Institutes of Health.
The University of Pennsylvania Medical Center's sponsored research and training ranks third in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $175 million in federal fiscal year 1997. In addition, for the third consecutive year, the institution posted the highest annual growth in these areas -- 17.6 percent -- of the top ten U.S. academic medical centers.
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Contact: Franklin Hoke
hokef@mail.med.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
5-Mar-1999