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Molecular biology

The navigator presses the start button

Munich, 11/19/2012

Gene transcription of DNA sequences into mRNA molecules is central to all forms of life. A new study shows that the molecular navigator that locates protein-coding sequences also gets transcription started.

Cellular DNA contains coded instructions for protein synthesis, and the sequences that specify protein structures are selectively transcribed into mRNA molecules. Since proteins perform most molecular transformations in cells, gene transcription is crucial for cell function. RNA polymerase II (Pol II), the enzyme responsible for transcription of protein-coding genes, is guided to transcription start sites in the nuclear DNA by the protein TFIIB. “Without this factor, transcription can not take place,” says Professor Patrick Cramer, Director of the Gene Center at LMU. In a new study, he and his coworkers show that TFIIB doesn’t just act as a navigator that leads Pol II to its sites of action.

Structural switch gives the start signal
In order to elucidate the role of TFIIB in the initial steps in gene transcription, Professor Cramer’s team used X-ray crystallography to determine the three-dimensional structure of the molecular complex formed by Pol II and TFIIB in association with DNA and mRNA. Much to the researchers’ surprise, the structure revealed that TFIIB itself alters the conformation of the active center of Pol II in such a way that transcription is stimulated. Functional studies confirmed the transcription factor’s stimulatory effect.

“Our observations explain why RNA polymerase, in contrast to the DNA polymerases that replicate the genetic material, does not require a short preformed nucleic acid – a so-called primer – to get started,” says Cramer. “These results are of fundamental significance to molecular biology and molecular genetics, as they enable us to understand an otherwise puzzling element of transcription, without which our genes would be forever silent.” (Nature, 14. November 2012) göd

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