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A Genomewide Search for Ribozymes Reveals an HDV-Like Sequence in the Human CPEB3 Gene
Kourosh Salehi-Ashtiani,1,2*Andrej Lupták,1*Alexander Litovchick,1Jack W. Szostak1
Ribozymes are thought to have played a pivotal role in the earlyevolution of life, but relatively few have been identified inmodern organisms. We performed an in vitro selection aimed atisolating self-cleaving RNAs from the human genome. The selectionyielded several ribozymes, one of which is a conserved mammaliansequence that resides in an intron of the CPEB3 gene, whichbelongs to a family of genes regulating messenger RNA polyadenylation.The CPEB3 ribozyme is structurally and biochemically relatedto the human hepatitis delta virus (HDV) ribozymes. The occurrenceof this ribozyme exclusively in mammals suggests that it mayhave evolved as recently as 200 million years ago. We postulatethat HDV arose from the human transcriptome.
1 Howard Hughes Medical Institute, Department of Molecular Biology, and Center for Computational and Integrative Biology (CCIB), 7215 Simches Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. 2 Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: szostak{at}molbio.mgh.harvard.edu
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