Early-stage Gene Transcription Creates Access To DNA

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Early-stage Gene Transcription Creates Access To DNA

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/10/081006130459.htm

A gene contained in laboratory yeast has helped an international team

of researchers uncover new findings about the process by which

protein molecules bind to control sequences in genes in order to

initiate gene expression, according to findings reported in the

journal Nature.

Previously thought to be inert carriers of the genetic instructions

from DNA, so-called non-coding RNAs turn out to reveal a novel

mechanism for creating access to DNA required by transcriptional

activation proteins for successful gene expression, according to

Boston College Biology Professor Hoffman, a co-author of the

study with researchers from two Japanese universities.

The team focused on transcription, the first step in gene expression,

whereby the blueprint of a cell's DNA is first communicated and paves

the way for RNA to deliver their specific pieces of protein-

synthesizing genetic coding – essentially flicking the switch that

activates the gene.

Hoffman and his colleagues examined how the yeast cell senses its

cellular environment and makes decisions about whether or not to

express a gene, in this case fbp1, which encodes an enzyme. What they

found was a preliminary transcription phase with a flurry of switches

flicked " on " and then " off " as seen by the synthesis of non-coding

RNA before the final " on " switch is tripped.

The non-coding RNAs initiate over one thousand base pairs of

nucleotides along the DNA away from the known start site for this

gene. The group discovered that the process of transcribing non-

coding RNAs is required for the eventual production of the protein-

encoding RNA. The transient synthesis of these non-coding RNAs serves

to unfurl the tightly wound DNA, essentially loosening the structure

to allow for gene expression.

" This is a novel identification of one of the many ways gene

expression can be regulated, " said Hoffman. " It's a surprising

discovery of why there are all these RNA molecules being made in

cells that are not protein-encoding molecules. It is in fact the

process of making these molecules that leads to the protein-encoding

RNAs. "

The paper was co-authored by Hoffman and RIKEN Advanced Science

Institute scientists Kouji Hirota, Kazuto Kugou, Takehiko Shibata,

Kunihiro Ohta and their colleague Tomoichiro Miyoshi at the

University of Tokyo.

" I hope this leads others to find similar events occurring on other

genes, " said Hoffman. " A big part of this kind of work is

understanding that there are other potential mechanisms for gene

expression. "