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NSF PR 00-74 - October 12, 2000
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Putting Muscle in the Nucleus
Scientists have long pondered how, inside the nucleus
of a cell, long stretches of DNA are moved through
the huge enzyme factories that transcribe DNA's genetic
information into messages made of RNA. Now, for the
first time, a team of scientists from the University
of Illinois at Chicago has demonstrated the presence
of a "molecular motor" inside the nucleus, where it
appears to power the assembly line that forges RNA
messages off of the long DNA templates.
The finding is reported in the Oct. 13 issue of the
journal Science. The work was funded by the
National Science Foundation (NSF), the National Institute
of General Medical Sciences (one of the National Institutes
of Health), the Czech Ministry of Education and the
Academy of Sciences of the Czech Republic.
The motor molecule, called myosin-1, is a close chemical
relative of the myosin responsible for muscle contraction.
"When your heart beats, when you take a breath, when
you digest food or have a baby - anytime cells move
or divide - myosin is involved," says Primal de Lanerolle,
professor of physiology and biophysics at UIC, who
led the international team.
Myosin, well-known since the 1920s, is a protein found
in the cytoplasm of nearly every type of cell in the
body. It had never before been found in the nucleus.
DNA, on the other hand, resides in the nucleus, where
it is transcribed into the RNA messages that then
travel to the cytoplasm to guide the synthesis of
the proteins - like myosin - that do all the work
of the cell.
"This is a very significant development," said Eve
Barak, acting deputy director of NSF's Division of
Molecular and Cellular Biosciences. "The outcome of
this work really underscores the importance of supporting
'risky' science. What started out as a project to
substantiate a highly controversial observation -
myosin in the nucleus - has turned out to be an important
key for understanding just how cells perform the rather
formidable task of transcribing complex genetic information
via DNA."
Despite the fact that transcribing DNA is itself prodigious
work, many scientists did not believe that myosin
existed in the nucleus - indeed, no motor molecule
had ever been found there. "We had an uphill battle
to convince our colleagues," de Lanerolle said.
His team convincingly demonstrated myosin-1 in the
nucleus. They also showed that this myosin fits together
closely with a key component of the transcription
machinery and that it plays an active role in making
RNA.
The discovery is important for several reasons, de
Lanerolle said. "It offers insight into the DNA transcription
process at the molecular level and shows that transcription
and muscle contraction have certain similarities.
Consequently, it may be possible to use what we know
about muscle contraction to better understand this
key first step in gene expression."
Transcription is essential for cells to grow and divide,
de Lanerolle noted, so an improved understanding of
its molecular mechanism may prove useful in finding
new ways to treat cancers and other diseases.
Other authors of the Science paper include Lidija Pestic-Dragovich,
Ljuba Stojiljkovic, Grzegorz Nowak and Yunbo Ke, all
of UIC; Anatoly Philimonenko and Pavel Hozak of the
Institute of Experimental Medicine of the Academy
of Sciences of the Czech Republic; and Robert Settlage,
Jeffrey Shabanowitz and Donald Hunt of the University
of Virginia.
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