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Small RNA, Great Expectations

A group of China's top scientists recently called for a speed-up of research and development of a number of cutting-edge high technologies in China.

Their proposals, compiled in a document titled "High Technology Development Report," were submitted to the members of China's top legislature, the National People's Congress, who just completed their annual session in Beijing on Sunday.

The report, one of a set of three compiled by the Chinese Academy of Sciences (CAS) - China's top scientific research body, reviews advances in science and high technology over the past year.

For years, these annual reports have been regarded as one of the most authoritative sources of information on Chinese progress in science and high technology.

Top Chinese scientists were invited to review advanced research in their respective areas and provide strategic proposals for the nation in the report.

Coordinated and edited by a research team led by Mu Rongping, deputy director of the CAS Institute of Policy and Management, the report contains 42 research papers contributed by 71 researchers and experts.

Of the many proposals, Professor Li Yanda's call for speeding up China's research on small RNAs stands out as the most conspicuous.

Over the decades, biological research worldwide has largely focused on genes, the functional sections on DNA molecules that are believed to play the key role in regulating life.

The prominence given to genes was highlighted in the billion-dollar international Human Genome Project that was completed last year. The project succeeded in sequencing human DNA, opening a new chapter in biological research.

But things changed a bit only a couple of years ago, when another molecule that was once thought less prominent in regulating life, RNA, or ribonucleic acid, began to move onto center stage.

Several research groups discovered the so-called small RNA, which was hailed by leading scientific journals as forcing biologists to overhaul their vision of the cell and its evolution.

These tiny bits of genetic material were virtually unknown a decade ago but are now on the cutting edge of cell biology, and a better understanding of their function may form the basis for important advances in medicine, agriculture and other fields.

"For most biologists, genes used to be everything and they largely still are," said Li Yanda, a professor with Beijing-based Tsinghua University. "But the discovery of the small RNA's miraculous functions has made them the hottest research area at the moment."

He said the new findings will soon be opening doors for new advances in medicine, immunology and plant development, among many areas.

A comprehensive study of DNA, cell biology and genetics evolved steadily from the 1960s through the 1990s. Most of the work focused on conventional protein coding genes, of which there are thousands, according to Li.

They were easy to study and recognize, and that's what most molecular biologists spent their careers working on, he said.

During that time, most RNA was believed to merely take genetic "orders" from DNA, and through the processes of transcription and translation, help produce the proteins that give cells their function.

In 1993, the first small RNA was discovered, and at the time it was thought to be a biological oddball. It appeared to have some type of regulatory function in the cell but little was known about it then.

But research in this field has exploded in just the past year or two. It now includes analysis of micro-RNAs and small interfering RNAs, and other biochemical players, in both plants and animals.

It has been found they play a major role in gene "expression," or the molecular mechanisms controlling genes that are required for cells to turn into lung, liver, brain or other cells.

It is also now clear that small RNAs control how whole chromosomes, or regions of chromosomes, are activated or deactivated.

Small RNAs may also hold the key to understanding some types of genetic birth defects, thus paving the way for the study of new types of disease therapies. They also offer clues to plant development, exert influence upon the function of the immune system, help explain some cancers, the function of stem cells, and many other cellular functions.

The pioneering research has found that small RNAs consist mainly of micro RNAs and small interfering RNAs, both of which can stop the function of messenger RNA as an intermediary of gene expression.

Scientists estimated small RNAs in humans may number from 200 to 255, or around 1 percent of human genes.

In rice, Chinese scientists led by Chen Runsheng have found 160 small RNAs.

"The search is continuing and spreading into other species," Li said.

Micro RNAs bind to matching pieces of messenger RNA, turning it into a double strand and keeping it from doing its job. The process effectively stifles the production of the corresponding protein.

Interfering RNAs, discovered five years ago by researchers from the University of Massachusetts, are able to silence their corresponding genes.

Some scientists believe that RNA interference is a protective mechanism against viruses, which sometimes create double-strand RNA when they replicate.

The latest research has found that micro RNAs and small interfering RNAs were the same length and used much of the same mechanism.

Scientists also found that RNA interference is a faster way to turn off genes than other methods, such as creating so-called knockout mice that lack a particular gene. Scientists are also looking to use RNA interference to treat diseases.

A research project led by Dr Philip Sharp, Nobel-prize-winning biologist from the Massachusetts Institute of Technology, showed an interfering RNA corresponding to a specific region in the human genome can effectively inhibit the HIV from replicating, shedding new light on the treatment of AIDS.

Theoretically, small RNA interference may also be used to treat SARS, hepatitis and influenza, Li said.

To turn that idea into reality, a lot of work needs to be done to understand the basic mechanisms of small RNAs, more of which are being identified daily.

He suggested the country increase funding in this area and at the same time encourage the development of RNA medicine.

In this largely unknown RNA area, Chinese researchers may have more opportunities for breakthroughs than in the already deciphered DNA strands, Li said.

(China Daily March 16, 2004)

Discovery of Small RNAs Named No. 1 Scientific Breakthrough of 2002
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