CSHL scientists discover new way in which ubiquitin modifies transcriptional...( Cold Spring Harbor N.Y. During gene...)

Cold Spring Harbor, N.Y. During gene transcription the process inside the nucleus of cells by which DNA, the genetic material, is copied into RNA molecules a large, ever-changing multiprotein complex is enlisted to assist the DNA-copying enzyme in its challenging job.

Like an exquisitely choreographed dance, each step in the process has to be performed with precision, in order for the copy to be accurate and useful in subsequent events. These events culminate in a version of the RNA copy exiting the nucleus and serving as the template for the production of new proteins.

Scientists have documented a host of mechanisms involved in the assembly and behavior of the "helper" protein complex. A team at Cold Spring Harbor Laboratory (CSHL) has now discovered a mechanism, which, according to Professor William P. Tansey, Ph.D., "provides a paradigm for how the components [of the helper complex] could be disassembled and how the complex falls apart." Their results will appear in the December 16th issue of Proceedings of the National Academy of Sciences.

One of the mechanisms that influences critical interactions in transcription is called ubiquitylation. It involves the addition of small protein molecules called ubiquitin to other, larger proteins. When ubiquitin "tags" are added to these larger molecules, it has the effect of marking them for destruction. Tansey's team has previously characterized how the ubiquitin-triggered destruction of transcription factors proteins that help switch on genes was connected to the regulation of gene activity.

The addition of ubiquitin, however, was later found, in other contexts, to modify proteins in non-destructive ways, too. This suggested to Tansey the existence of a more benign link between transcription and ubiquitylation. Working with yeast cells, Tansey's team has now identified this link: a protein called Asr1.

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