Nature and the Nature Research Journals - Papers published online on 31 July 2005

Batten down the hatches; Faster sequencing of DNA; Targeting the transcription start site of DNA; A new way to silence genes.

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 31 July 2005

* Batten down the hatches - Nature
* Faster sequencing of DNA - Nature
* Targeting the transcription start site of DNA - Nature Chemical Biology
* A new way to silence genes - Nature Chemical Biology

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(http://www.nature.com/nature)

[1] Batten down the hatches

DOI: 10.1038/nature03906

Hurricanes have been getting more destructive over the past three decades, according to Kerry Emanuel in new research published online by Nature. He warns us that global warming might increase the effect of hurricanes further still in the coming years. Previous studies that have looked at the effects of rising global average temperatures on tropical cyclones - commonly called hurricanes or typhoons - have tended to focus on the issue of whether these events have become more frequent. No such trends have been clearly observed. But Emanuel looks instead at the question of whether cyclones have got more intense - that is, whether they hit harder and last longer. Theories and computer simulations of climate indicate that warming should indeed generate an increase in storm intensity. Emanuel has analysed records of tropical cyclones since the middle of the twentieth century, and finds that the amount of energy released in these events in both the North Atlantic and the North Pacific oceans has increased markedly since the mid-1970s. Both the duration of the cyclones and the largest wind speeds they produced have increased by about 50 per cent over the past 50 years.

Emanuel finds that these increases in storm intensity are mirrored by increases in the average temperature at the surface of the tropical oceans, suggesting that this warming - some of which can be ascribed to global warming - is responsible for the greater power of the cyclones. He points out that as the human population in coastal regions gets ever denser, the damage and casualties produced by more intense storms could increase considerably in the future.

Author contact:
Kerry Emanuel (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 2462/4089, Email: [email protected]

PLEASE NOTE: Prof. Emanuel is currently on vacation in France and will be contactable via email until Thursday 28 July when he will be travelling back to the USA. You will be able to contact him on his work contact details from Friday 29 July onwards.

[2] Faster sequencing of DNA

DOI: 10.1038/nature03959

US scientists have developed a one-hundred-times faster way to sequence DNA. The new method can sequence 25 million bases - the building blocks of DNA - in one four-hour run with 99 per cent or more accuracy, Jonathan Rothberg and colleagues report in a paper published online by Nature. The researchers achieved this feat by first amplifying and then sequencing hundreds of thousands of unique DNA molecules all at the same time in tiny reaction spaces that are on a plate measuring 60x60 square millimetres. The machine uses light to measure the sequencing reaction. The researchers used it to re-sequence the genome of the bacterium Mycoplasma genitalium (580,069 bases) in just one four-hour run. The method has the potential to become even faster in the future once it can be miniaturized to accommodate even more reactions, they write.

Author contact:
Jonathan Rothberg (454 Life Sciences Corp., Branford, CT, USA)
Tel: +1 203 871 2300, E-mail: [email protected]

**********NATURE CHEMICAL BIOLOGY*****************
(http://www.nature.com/nchembio)

[3] Targeting the transcription start site of DNA

DOI: 10.1038/nchembio724

A new method of silencing gene expression is reported in the September issue of Nature Chemical Biology. By targeting DNA transcription start sites with peptide nucleic acids (PNAs) researchers have blocked a protein connected to the spread of certain tumours. When bound to the human progesterone receptor (hPR) start site, PNA blocks hPR production, resulting in the upregulation of ezrin, a protein associated with the metastasis of some tumours. Transcription-the conversion of genes into RNA copies-is initiated at sites where polymerase enzymes bind to DNA. Corey and coworkers hypothesized that these transcriptional start sites may be ideal targets for gene silencing approaches. To demonstrate their approach, they targeted the transcription start site of the hPR DNA with an antigene PNA (agPNA). agPNAs directed toward one form of the receptor, hPR-B, potently inhibited hPR-B mRNA production, but also reduced the mRNA levels of hPR-A, a receptor variant.

These results suggested an unknown regulatory link between hPR-B and hPR-A expression. Downregulation of hPR in tumor cells by agPNAs changed cell development and enhanced the expression of ezrin, a cytoskeletal protein known to be involved in the metastasis of certain tumors.

The authors showed the usefulness of their approach by blocking gene transcription in live diseased cells, allowing direct observation of the effects of gene silencing. Because every gene contains a DNA transcription start site, this method of controlling transcription initiation could offer a powerful tool for studying cellular processes and potentially treating diseases such as cancer.

Author contact:
David R. Corey (University of Texas Southwestern Medical Center, Dallas, TX, USA)
Tel: +1 214 645 6155, E-mail: [email protected]

Additional contact for comment on paper:
Bruce Armitage (Carnegie Mellon University, Pittsburgh, PA, USA)
Tel: +1 412 268 4196, E-mail: [email protected]

[4] A new way to silence genes

DOI: 10.1038/nchembio725

The ability to shut down the expression of a particular gene of interest would not only provide a powerful tool for studying cellular processes but could also have the potential to treat certain diseases such as cancer. In the September issue of Nature Chemical Biology, researchers describe a new approach to gene silencing by targeting the transcription start site of DNA.

The synthesis of a protein begins with the transcription of its corresponding DNA by an enzyme called RNA polymerase II to generate a strand of messenger RNA, which carries the DNA template information out of the cell nucleus to the cytoplasm. mRNA is in turn translated by ribosomes, which generate the appropriate amino acid sequence of proteins.

Scientists have investigated ways of disrupting this process as a means of studying cellular processes or disease states. Corey and co-workers hypothesized that the transcription start site of double stranded DNA would make an ideal target for gene silencing as it plays a critical role in initiating transcription. The team prepared sequences of RNA called antigene RNA (agRNA) designed to form a complementary pair with the corresponding transcription start site DNA and block its transcription. They found that agRNAs corresponding to the start site of one form of the human progesterone receptor (hPR-B) are potent inhibitors of hPR-B mRNA production. They also showed the power of their technique by targeting three other gene transcription start sites with corresponding agRNA strands. In each case, they observed potent downregulation of mRNA production.

Because every gene contains a DNA transcription start site, the targeting of these structures using readily available RNA sequences, like RNA interference, offers potential as a research tool or for therapeutic approaches that block gene expression.

Author contact:
David R. Corey (University of Texas Southwestern Medical Center, Dallas, TX, USA)
Tel: +1 214 645 6155, E-mail: [email protected]

Additional contact for comment on paper:
Bruce Armitage (Carnegie Mellon University, Pittsburgh, PA, USA)
Tel: +1 412 268 4196, E-mail: [email protected]

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Items from other Nature journals to be published online at the same time:

NATURE GENETICS (<http://www.nature.com/naturegenetics>)

[5] Gene duplication and exon shuffling by helitron-like transposons generate intraspecies diversity in maize
DOI: 10.1038/ng1615

[6] Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation
DOI: 10.1038/ng1614

NATURE NEUROSCIENCE (<http://www.nature.com/natureneuroscience>)

[7] Neural basis of auditory-induced shifts in visual time-order perception
DOI: 10.1038/nn1512

[8] Neural codes for perceptual discrimination in primary somatosensory cortex
DOI: 10.1038/nn1513

[9] Reductions in neural activity underlie behavioral components of repetition priming
DOI: 10.1038/nn1515

NATURE IMMUNOLOGY (<http://www.nature.com/natureimmunology>)

[10] Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses
DOI: 10.1038/ni1233

[11] Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism
DOI: 10.1038/ni1234

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GEOGRAPHICAL LISTING OF AUTHORS

The following list of places refers to the whereabouts of authors on the
papers numbered in this release. The listing may be for an author's main
affiliation, or for a place where they are working temporarily. Please see
the PDF of the paper for full details.

CANADA
Burnaby: 7
Toronto: 11

CHINA
Beijing: 6

ITALY
Milan: 5
Rome: 7
Udine: 5

MEXICO
Mexico City: 8

UNITED STATES OF AMERICA
Arizona
Tucson: 5
California
Berkeley: 2
La Jolla: 7, 10
San Diego: 10
Connecticut
Branford: 2
Guilford: 2
Farmington: 6
Groton: 6
Delaware
Wilmington: 5
Massachusetts
Cambridge: 1
Missouri
Kansas City: 6
New Hampshire
Hanover: 9
New York
Cold Spring Harbor: 8
New York: 2, 6
Texas
Dallas: 3, 4
San Antonio: 6

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Published: 31 Jul 2005

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