How a Search for Promoters Led to the Discovery of Introns and Exons


Richard J. Roberts

New England Biolabs

 

Serendipity has played a major role in my scientific life. A quick Ph.D.in chemistry gave me the time to discover molecular biology while reading John Kendrew’s book “The thread of life” in the Sheffield library.  This was followed by a post-doc at Harvard instead of Wisconsin, an RNA sequencing project that led to a lifelong interest in sequences and a chance attendance at a seminar by Dan Nathans, which peeked my interest in restriction enzymes. At Cold Spring Harbor my laboratory initiated a search for more than the handful of restriction enzymes known in 1973 and we were extremely successful, finding more than 70% of the first 100 such enzymes discovered. In 1975 Richard Gelinas joined my lab as a postdoc and decided to try and characterize a eukaryotic promoter. We found a new way to approach this problem based on characterizing the 5’-ends of mRNAs. However, almost immediately the approach we had chosen gave unexpected results about the structure of Adenovirus-2 (Ad2) mRNAs. The results could only be explained if mRNA production in Ad2 was fundamentally different than that found in bacteria and their phages. Not only was the mRNA synthesis different, but the structure of the genes was different too. Thanks to a collaboration with Louise Chow and Tom Broker the difference became easily visualized, showing the genes were split into introns and exons. Throughout my career, luck and the opportunity to follow through on unexpected results has been crucial to my success.






 

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