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.
Media contact:
Tom Garritano
(703) 292-8070/tgarrita@nsf.gov
Program contact:
Eve Barak
(703) 292-8442/ebarak@nsf.gov