While the entire gene is copied into pre-mRNA, not all of that information will be used to make a protein. RNA segments called exons carry the protein-making information, while the segments between exons, called introns, are snipped out of pre-mRNA by special proteins. Exons also may be snipped out. Once snipping is complete, the remaining exons are spliced back together to form a fully functional, mature mRNA molecule, which goes on to create a protein.
Using computers, the UT Southwestern researchers scanned the human genome and found that the presence of certain DNA sequences called "tandem repeats" that lie between exons are highly correlated with the process of alternative splicing. They found a large number of tandem repeats on either side of exons destined to be spliced out of the pre-mRNA. The tandem repeat sequences also were complementary and could bind to each other.
"The complementary tandem repeat sequences on either side of an exon allow the DNA to loop back on itself, bind together, pinch off the loop containing a particular exon and then splice it out," Dr. Garner explained.
The chemical units that make up an organism's DNA are abbreviated with the letters A, C, T and G. Strings of these letters form genes and spell out genetic instructions. Tandem repeats have DNA sequences with the same series of letters repeated many times, such as CACACACACACA.
Tandem repeats are "hot spots" where errors can easily be made during the copying process; for example, an extra CA could be added or deleted from the correct sequence. These errors could then result in a gene improperly splicing out an exon, thus making the wrong protein, Dr. Garner said. His research group has previously shown that these sequences are highly variable in cancer, and he said the new findings could go a long way toward understanding the genetic nature of how can
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
14-Apr-2005