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New 3-D model of RNA 'core domain' of enzyme telomerase may offer clues to cancer, aging
Date:11/4/2010

then did biochemical studies that showed that the bend and its flexibility is important for telomerase activity. The internal bulge loop turns out to be really important in determining the topology of this domain, which was unpredicted."

"We are learning how the internal bulge loop functions, and we have characterized its role in the catalytic activity," said Zhang, who holds a Baltimore Family Fellowship from the Life Sciences Research Foundation.

The structure and dynamics of the internal bulge loop are important for catalytic activity.

"We have found a rare structure," Feigon said. "We studied the database of all the structures of RNA that have been solved, and it turns out that one other structure has the same type of five-nucleotide bulge. The other one is from an RNA domain of the hepatitis C virus. That was a huge surprise for us. And the bigger surprise is that the nucleotide sequence of that bulge is completely different, but the structure is almost identical. That particular bulge is also critical to the function of the virus; if you disrupt that bulge, the hepatitis C virus becomes less infectious."

For telomerase to be active, it needs the telomerase RNA and a protein called human telomerase reverse transcriptase. Chromosomes are composed of strings of bases -- nucleotides-- represented by the letters A, C, G and T. The 'C' base always binds to 'G,' while 'A' binds to 'T.' The bases combine to make three-letter codes that specify an amino acid; the corresponding amino acids combine to make proteins.

"Within telomerase, there is an RNA template that is used to code for the telomere DNA repeats," Feigon said. "If you have the letter 'A,' it puts in the letter 'T,' and if you have a 'G,' it puts in a 'C.' This method of copying, from RNA to DNA instead of copying DNA to RNA, is called reverse transcription. The core domain includes the template which does this. HIV also has a reverse transcriptase that
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Contact: Stuart Wolpert
swolpert@support.ucla.edu
310-206-0511
University of California - Los Angeles
Source:Eurekalert

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