Menu
Biology articles
The Golden Goose Is Awarded
Salmonella Strain Spreads Alongside HIV
Fair Flu Viruses Closely Matched
Creative Emulsification
Inflammation for Regeneration
Editor's choice in microbiology
Debate Over Stem Cell Effectiveness
Editor's choice in molecular biology
Telomeres Affect Gene Expression
Re-sensitizing Resistant Bacteria
Vitamin C Slays TB Bacteria
Plant scientists, innovators
The First Plant Interactome
Plant RNAs Found in Mammals
Opinion: Beyond the Model
Sweet and Sour Science
Plant RNA Paper Questioned
Flower Barcodes
Microbial Perfume
How Plants Feel
New Databases Harvest a Rich Bounty of Information on Crop Plant Metabolism
Carnegie Institution for Science Receives Grand Challenges Explorations Grant
Genetically engineered trees could help restore devastated American chestnut
Evolution coup: study reveals how plants protect their genes
  Plant RNA Paper Questioned
When the news broke last September about a study identifying small RNAs from ingested plants in animals, the focus shifted unexpectedly and quickly to potential implications for genetically modified (GM) food safety. But some experts in the field of RNA interference (RNAi) feared that the GM-related concerns were misplaced, and that there were more fundamental issues with the research.

The research team, led by Chen-Yu Zhang of Nanjing University, China, reported finding small RNA molecules from ingested rice and other plants in the bloodstream of both mice and humans and in mice livers. One of these RNAs from rice, they found, could inhibit a mouse protein that usually aids in removal of LDL or “bad” cholesterol from the blood.

The controversy surrounding the results started even before publication. An editor at Science, for example, rejected the manuscript because the discovery was “too extraordinary,” Zhang says—a response the group also received from Cell and Molecular Cell. The journal Cell Research accepted the report after a 2-year effort that included, according to Zhang, eight months of added experimental work to address reviewer critiques. Then, publication of the findings triggered concerns that small RNAs ingested from plants could affect how our bodies function, and unpredictable alterations in these molecules in GM plants might have unpredictable effects.

But RNAi expert Phillip Zamore, investigator at the Howard Hughes Medical Institute and Gretchen Stone Cook Professor of Biomedical Sciences at the University of Massachusetts Medical School, thinks that rushing to any conclusions about GM relevance is premature. “If you could dream up a molecule that you would worry about [for GM foods], this wouldn’t be it,” he said.

The deeper question, Zamore said, lies in the assertion that single-stranded RNA molecules like these microRNAs, or miRNAs, which silence expression of their RNA targets, can survive the digestive tract. They are “very fragile,” he said. The idea that these RNAs would not be immediately destroyed by the digestive enzymes of the gut “is controversial, to say the least,” he added. “Hundreds of millions of dollars have been spent trying to stabilize single-stranded nucleic acids in the bloodstream, let alone the digestive tract, and unmodified RNA has never been found to survive.”

But Zhang disagreed, pointing to a 2008 paper in which he and his colleagues demonstrated that endogenous animal miRNA could exist stably in the bloodstream, suggesting that blood-borne miRNAs somehow resist being broken down. So the new findings that miRNA from plants can be stable in blood or other tissues are not unprecedented, he argued. These latest results also raise the “surprising possibility that miRNAs derived from plants are especially stable, although this will need to be confirmed by others,” said plant biologist Eric Lam, a professor at Rutgers State University. Lam also noted that the miRNAs in question were ingested as part of plant tissues, not as unprotected RNAs, a possible explanation for their ability to survive the animal digestive tract.

Zamore is also concerned about the potential for cross-detection between plant and animal RNA sequences, given the short length of miRNA molecules, which average about 22 nucleotides, he said. “There’s a real likelihood that there will be at least one sequence in (the mouse or human) genome that matches the sequence from the plant.” As a result, the Zhang team’s findings could reflect degraded animal RNA sequences, rather than plant miRNA, he said, adding that the study design allowed for one mismatch within the detected sequences, increasing the likelihood of a fortuitous cross-detection.

Lam believes otherwise. While mismatching is “possible,” he said, it’s “not very likely.” Zhang added that the group performed an analysis for a chemical signature specific to plant miRNAs that “clearly demonstrated (that) serum miRNAs we detected were the exogenous plant miRNAs.”

Even if one accepts the premise that the RNAs identified in the study were, in fact, of plant origin, however, Zamore questions whether the levels detected have any meaningful impact on the animals. For miRNAs to be effective as interfering RNAs, Zamore said, they must be present in a quantity sufficient to match the quantity of the RNA targeted for silencing. “MicroRNAs function in cells at remarkably high levels,” he said. “For example, miRNA-122, which controls cholesterol production in the liver, is present at a half million molecules per cell.” The Zhang paper describes detecting the equivalent of just 853 copies per cell.

But Zhang argues that even these low levels are relevant, referring to previous studies that have identified “biologically active” levels of miRNAs ranging from 700 to 4,450 copies per cell. Lam noted that the relevant number probably depends on the specific RNA molecule. “It is at least possible that some small RNAs are more potent than others,” he said.

One thing that Zhang, Zamore, and Lam seemed to agree on is that unanswered questions remain, such as whether the RNAs are further modified in some way to pass digestion and how they affect human physiology. Indeed, Zhang says that the editor who rejected the paper as “too extraordinary” expressed interest in the group’s “next similar story.” Given the interest the first installment has generated, the editor won’t be alone in that interest.
Plants Put Limit on Ice Ages
Carnegie donates landmark clones to biology
Plants on Steroids: Key Missing Link Discovered
Gene Function Discovery: Guilt by Association
Cracking the Plant-Cell Membrane Code
Private Support Helps Public Plant Research
Scientists Watch Cell-Shape Process for First Time
How plants choose their mates
Mastermind Steroid Found in Plants
Unlocking the secrets of a plant’s light sensitivity
Nailing down a crucial plant signaling system
What makes a plant a plant?
New component of a plant steroid-activated pathway discovered
Big Boost to Plant Research
The Heart of the Plant
New tool offers unprecedented access for root studies
Steroids control gas exchange in plants
Plant toughness: Key to cracking biofuels?
Amoeba may offer key clue to photosynthetic evolution
The future of plant science – a technology perspective
Plant research funding crucial for the future
Wolf B. Frommer Receives Bogorad Award for Excellence in Plant Biology
Lighting up the plant hormone “command system”
Plant organ development breakthrough
Breakthrough: How salt stops plant growth
New Cancer Diagnostic Technique Debuts
Plant Science Could Ease Global Food and Fuel Demands
Have you had your cereal today?
Menu
Researchers close in on engineering recognizable, drug-free Cannabis plant
UC Riverside Researchers Develop Genetic Map for Cowpea
New research shows how mobile DNA survives—and thrives—in plants, animals
Cucumber Genome Published
Structural study at EMBL reveals how plants respond to water shortages
“Safety Valve” Protects Photosynthesis from Too Much Light
Weeds Could Help To Feed The World
Antagonistic Genes Control Rice Growth
Making New Enzymes to Engineer Plants for Biofuel Production
Green Plant Transport Mystery Solved
Gene Discovery To Increase Biomass Needed For Green Fuel
Are genes our destiny?
New African cassava resists devastating viruses
Species richness and genetic diversity do not go hand in hand in alpine plants
Scientists discover how cancer may take hold
Green algae—the nexus of plant/animal ancestry
New Twist on Life’s Power Source
Controlling a sea of information
Plant Steroids Offer New Paradigm for How Hormones Work
Future of biology rests in harnessing data avalanche
Carnegie’s Arthur Grossman Receives Gilbert Morgan Smith Medal
Plant Scientists Participate in DOE Energy Frontier Research Center
Advance in understanding cellulose synthesis
Midget Plant Gets Makeover