Now that high school biology students can recite that genes are made of
DNA, which is transcribed into messenger RNA (mRNA), which is then
translated into protein, along comes a new class of molecules, sending
students?and many scientists?scrambling for updated textbooks.
A study by Salk Institute for Biological Studies investigator Joseph
Ecker, Ph.D., reported in the May 15, 2008 online issue of Developmental
Cell, shows that the RNA world is more complex than imagined. Ecker and
colleagues tinkered with factors that process mRNAs in the mustard weed
Arabidopsis thaliana and observed affects on short, or small RNAs. Their
findings could impact fields as diverse as plant pathology and cancer
research.

Although they don?t fit neatly into the DNA-to-mRNA-to-protein
progression, small RNAs or microRNAs are the next big thing in both
plant and animal molecular biology. Discovered a decade ago, numerous
studies show that small RNAs put the brakes on the mRNA-to-protein step,
by latching onto mRNA and blocking its translation into protein or
causing its destruction, a phenomenon called RNA silencing.

Ecker, a professor in the Plant Biology Laboratory and director of the
Salk Institute Genomic Analysis Laboratory, started by posing a simple
genetic question. Researchers knew that eliminating either one of two
proteins?one an mRNA-degrading enzyme called EIN5, and another a protein
called ABH1 that binds to and protects mRNA from degradation?caused
developmental defects in plants. Ecker?s group asked what the effects of
mutating both simultaneously might be.

Aided by revolutionary ?deep-sequencing? technology, which detects rare
RNAs at high resolution, the investigators combed through the collection
of all small RNAs?known as the ?smRNAome??and found that ein5/abh1
double mutant plants ramped up small RNA levels just enough to reveal
something not seen before: the mutant plant cells were churning out
small RNAs made from some of their own protein-coding mRNAs.

Investigators already knew that plants defend themselves against
invading pathogens like viruses by generating short RNAs that recognize
and silence foreign viral RNA. Observing that plants may silence their
own RNAs in this manner was unanticipated. ?Our study shows that the way
plants regulate RNAs produced in viruses is also probably the way they
regulate their own genes,? said Ecker. ?This has not been shown before
in any organism?plant or animal.?

Ecker thinks this type of mRNA silencing is not an aberration of
ein5/abh1 mutant plants. ?What we are seeing is in these mutants is
probably a generic phenomenon that will likely hold true across all
systems,? said Ecker.

And why have these types of small RNAs not been observed before"
Probably because researchers have not had the tools?namely, the ?right?
mutants scrutinized by powerful new sequencing technology?to detect them
until now.

Brian D. Gregory, Ph.D., a postdoctoral fellow in the Ecker lab and
first author of the paper, feels that understanding small RNA
activity?whether in a plant or animal cell setting?has implications for
cancer research, a connection you might expect a plant biologist who is
also recipient of the highly prestigious Damon Runyon fellowship for
cancer research to make.

?What we learn about RNA silencing pathways in plants could be applied
to cancer chemotherapy,? Gregory explained. ?There are genes expressed
in tumor cells that protect them from being killed by chemotherapy?we
might be able to use small RNAs to antagonize the effect of these genes
in cancer cells.?

Ecker also sees the study as particularly timely in terms of ecological
change. ?If you understand how plants respond normally to pathogens, you
can rapidly make changes in that response,? he said. ?If climate change
occurs there is no doubt that insect pest populations will shift, and
insects are what transmit viruses. Those insects will likely move into
areas they have not seen before. Since small RNAs evolved to target
invading pathogens, manipulating them may combat these effects.?

Other authors contributing to the study include Ronan C. O'Malley,
Ph.D., Ryan Lister, PhD., Mark A. Urich, and Huaming Chen?all in the
Ecker lab?and Julian Tonti-Filippini and Harvey Millar, Ph.D., both at
ARC Centre of Excellence in Plant Energy Biology at the University of
Western Australia, Perth.

The Salk Institute for Biological Studies in La Jolla, California, is an
independent nonprofit organization dedicated to fundamental discoveries
in the life sciences, the improvement of human health and the training
of future generations of researchers. Jonas Salk, M.D., whose polio
vaccine all but eradicated the crippling disease poliomyelitis in 1955,
opened the Institute in 1965 with a gift of land from the City of San
Diego and the financial support of the March of Dimes.

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