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Unique change in protein structure guides production of RNA from DNA
Date:11/7/2013

mammals, the researchers took a closer look.

The first breakthrough came when the research team identified a new type of modification, known as acetylation, which regulated transcription.

"Our next breakthrough occurred when we pinpointed the precise locations on the CTD where acetylation occurredand realized it was unique to higher eukaryotes," explained Sebastian Schrder, PhD, the paper's first author. "We then wanted to see how this mammalian-specific acetylation fit into the realm of polymerase pausing."

Now that the team knew where the CTD became acetylated, their next goal was to find out when. Clues to the timing of acetylation came in experiments where they mutated RNAPII so that CDT was unable to become acetylated. In these cases, the length of polymerase pausing dropped, and the necessary steps for the completion of transcription failed to occur. Additional experiments revealed the elusive timeline of acetylation and transcription.

"RNAPII binds to DNA to prepare for transcription. Shortly after that we see polymerase pausingat which point the CTD becomes highly acetylated," continued Dr. Shrder. "Soon after the pause, CTD is then deacetylatedthe original modification is reversedand transcription continues without a hitch."

Polymerase pausing is not unique to mammalsin fact it was characterized in HIV, the virus that causes AIDS, many years agobut the fact that the CTD becomes acetylated just before or during the time when transcription is paused appears to be unique. Drs. Ott and Schrder argue that CTD acetylation is a stabilizer, preparing RNAPII for efficient completion of transcription and slowing down the process to make sure everything is functioning correctlynot unlike the final 'systems check' a pilot must perform before takeoff.

These findings offer important insight into the relationship between acetylation and transcription. And given the importance of transcription in the growth and maturat
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Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Source:Eurekalert  

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