Scientists determine how precursors of gene-regulating small RNAs are sorted by cellular machinery

Jan 04, 2010

A team of scientists at Cold Spring Harbor Laboratory (CSHL) has determined a hierarchical set of criteria that explain how the molecular precursors of gene-regulating small RNAs are sorted by the cellular machinery.

Led by Benjamin Czech, a group working in the laboratory of CSHL Professor Gregory Hannon posed the question: can distinct patterns be observed in the process that unfolds when double-stranded RNAs enter the RNAi pathway? Shorthand for , RNAi is a biological response to double-stranded RNA that can culminate in the regulation of . It has been observed in a vast range of organisms ranging from plants to worms to flies to man.

An enzyme called Dicer cuts double-stranded RNAs into smaller double-stranded pieces called duplexes. Czech, Hannon and colleagues propose rules governing the next step in the RNAi pathway, in which duplexes are sorted to proteins called Argonautes which are at the core of a molecular complex called RISC (the RNA-Induced Silencing Complex).

"Only one strand of each duplex is chosen," explains Czech, "and which one makes all the difference. In the fruit flies that we used as models for this series of experiments, the selection of one or another strand effectively determines whether the short will seek out and regulate a gene, or whether it will perform another function such as protecting a cell against a viral invader."

The rules determining how a duplex is processed and sorted are discussed in a paper the team published recently in Molecular Cell. These include the overall arrangement of the in the duplex; how many bases are paired; where they're paired and unpaired; and how tightly the ends of the duplex are stuck together.

"These rules for sorting are important for two reasons," according to Hannon, who is also an Investigator of the Howard Hughes Medical Institute. "One is that since small RNAs play critical biological roles in nearly every process, understanding which strands of the small RNAs entering RISC act as regulators of gene expression is critical for our fundamental understanding.

"The rules are also important because scientists are hoping to use small RNAs one day as therapeutics. By understanding the rules by which small RNAs are processed and sorted, we move closer to the goal of being able to manipulate the RNAi pathway, bend it to the purpose of addressing disease."

Explore further: Fighting bacteria—with viruses

More information: "Hierarchical Rules for Argonaute Loading in Drosophila" appeared in Molecular Cell, Vol. 36, No. 3. The authors are: Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf gordon, Norbert Perrimon and Gregory J. Hannon.

Related Stories

Silence of the genes

Oct 13, 2009

The molecular architecture of a protein complex that helps determine the fate of human cells has been imaged for the first time by researchers with the U.S. Department of Energy's Lawrence Berkeley National ...

The RNA drug revolution -- a new approach to gene therapy

Jan 23, 2008

RNA interference (RNAi) represents an innovative new strategy for using small RNA molecules to silence specific genes associated with disease processes, and a series of review articles describing the state-of-the-art and ...

Biologists Develop Large Gene Dataset for Rice Plant

Mar 13, 2007

Scientists have reported development of a large dataset of gene sequences in rice. The information will lead to an increased understanding of how genes work in rice, an essential food for much of the world's ...

Scientists get first detailed look at Dicer

Jan 13, 2006

Scientists have gotten their first detailed look at the molecular structure of an enzyme that Nature has been using for eons to help silence unwanted genetic messages. A team of researchers with Lawrence Berkeley ...

Recommended for you

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0