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Tandem transcripts team together

In the January issue of the journal Genome Research, two teams of scientists describe a widespread phenomenon in the human genome called transcription-induced chimerism (TIC), where two adjacent genes produce a single, fused RNA transcript. The work has implications for drug development, as well as for understanding mechanisms underlying gene evolution, transcription regulation, and genomic organization.

Dr. Roderic Guig's group from the Centre de Regulaci Genmica (Barcelona, Spain), in collaboration with the group of Dr. Stylianos Antonarakis from the University of Geneva (Switzerland), and Dr. Rotem Sorek's team from Compugen (Tel Aviv, Israel) independently derived estimates that at least 2-5% of the genes in the human genome are involved in these events.

"In a certain way, this phenomenon challenges our very concept of a gene," points out Guig. "The 'one gene, one protein' rule has been fundamental to molecular biology. However, as we deepen our understanding of the eukaryotic genome, a picture emerges that challenges this paradigm not a picture in which the sequences in the genome have distinct functions, but rather one in which the sequences participate in multiple transcripts, encoding molecules with diverse functionality."

Sorek's team systematically identified over 200 cases of TIC involving 421 human genes. They found that genes involved in TIC events often reside closer together than other gene pairs in the genome. In addition, they discovered that the intergenic sequences of TICs were processed via the same standard eukaryotic splicing machinery that removes introns from RNA transcripts.

Following a similar whole-genome survey of splicing events, Guig's laboratory focused on the ENCODE regions, a set of DNA sequences, representing 1% of the genome, that have been chosen by a large research consortium for more rigorous, in-depth analyses. When focusing on these regions, the researchers identified six TIC event
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Contact: Maria Smit
smit@cshl.edu
516-422-4013
Cold Spring Harbor Laboratory
4-Jan-2006


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