RNA emerges from DNA's shadow

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RNA emerges from DNA's shadow

http://www.eurekalert.org/pub_releases/2008-07/esf-ref071008.php

EUROCORES program RNAQuality holds first conference

RNA, the transporter of genetic information within the cell, has

emerged from the shadow of DNA to become one of the hottest research

areas of molecular biology, with implications for many diseases as

well as understanding of evolution. But the field is complex,

requiring access to the latest equipment and techniques of imaging,

gene expression analysis and bioinformatics, as well as cross-

pollination between multiple scientific disciplines. This has led to

a major European push to bring the field together via a network of

overlapping multidisciplinary projects, spearheaded by the European

Science Foundation (ESF) with its EUROCORES Programme RNAQuality.

The great potential of the RNA research field to solve a variety of

fundamental problems relevant for understanding of life and

predicting cures for diseases was unleashed at the RNAQuality

Programme's first conference, held in Granada in June 2008. As well

as many European groups, the conference was represented by leading

pioneers from the US in the field, who welcomed the new initiative as

an important collaborative force.

RNA was once considered to be just the faithful messenger taking

genetic information from the genome to the ribosome, or protein

factory, but that view has been blown away by recent research. It is

now known that RNA has additional roles in regulating gene expression

and as an important structural component both in the cell nucleus and

in the ribosomes. Furthermore, errors in transcribing RNA from DNA

are frequent and require a variety of elaborate quality control

mechanisms to prevent both mis-regulation of genes, and manufacture

of aberrant RNA and protein fragments that clog up the workings of

the cell, and that if unchecked can cause a variety of disorders,

including cancers.

Delegates at the conference also heard how there is great potential

for creating new compounds that manipulate the cell's apparatus for

transcribing DNA into RNA to overcome a number of serious disorders

caused by deleterious mutations in specific genes, as opposed to

problems with the RNA itself. son also presented one of the most

exciting developments, a molecule that overcomes a common deficiency

in genes that prevents their being read right up to the end of their

sequence during transcription. son pointed out that there are

about 2400 human genetic disorders resulting from mutations that

cause genes to be incompletely read, including cystic fibrosis and

muscular dystrophy. A drug based on the molecule is now entering

trials that could lead to it becoming generally available. Results so

far indicate dramatic improvements in both cystic fibrosis and

muscular dystrophy sufferers, although it is only suitable for those

disorders caused by the presence of a premature stop sign in a gene

sequence, as a result of a mutation. It does though highlight the

huge therapeutic potential of the research into RNA and its quality

control.

Significant progress has been made in different aspects of RNA

research over the last decade or more, leading to the current

situation where many groups are working on different aspects of the

problem. The challenge being met by the ESF's RNAQuality Programme is

to bring these groups together, and make Europe a much greater force

in the field, according to Jim , from Marquette University's

Department of Biological Sciences in the US.

Another important aspect of RNA research lies in the interaction

between DNA transcription, and the physical structure both of the

membrane-bound cell nucleus and the genome coiled within it. Genes

are transcribed within the nucleus and the resulting RNA molecules

then emerge through small holes that are connected to the genome by

proteins called nuclear pore complexes. In one of the presentations,

Nick Proudfoot from Oxford University in the UK explained how some

genes are enhanced by being close to the nuclear pore complex,

indicating a close relationship between gene expression and nuclear

structure that must have played out through evolutionary history.

Another point to emerge from Proudfoot's presentation was how some

genes are expressed more efficiently for a different reason, because

the section of DNA containing their sequence is coiled locally into a

loop, rather than as a branch. Quite simply, this speeds up the

transcription process of reading the gene because the enzyme

concerned, RNA Polymerase, can just keep on encircling the loop. As

Proudfoot explained, this is relevant for quality control as

well. " They may afford quality control by " telling " the polymerase it

is transcribing a bona fide gene, with a proper beginning and end, "

said Proudfoot. " Otherwise the polymerase may have initiated

erroneously. " The existence of a DNA ring makes it easier to identify

the sequence corresponding to a gene, and transcribe it correctly.