j*****d
发帖数: 787 | 1 http://the-scientist.com/2011/09/20/plant-rnas-found-in-mammals
+Plant RNAs Found in Mammals
MicroRNAs from plants accumulate in mammalian blood and tissues, where they
can regulate gene expression.
By Cristina Luiggi | September 20, 2011
11 Comments Link thisStumbleTweet thisDreamstime.com, Rewat
WannasukMicroRNAs from common plant crops such as rice and cabbage can be
found in the blood and tissues of humans and other plant-eating mammals,
according to a study published today in Cell Research. One microRNA in
particular, MIR168a, which is highly enriched in rice, was found to inhibit
a protein that helps removes low-density lipoprotein (LDL) from the blood,
suggesting that microRNAs can influence gene expression across kingdoms.
“This is a very exciting piece of work that suggests that the food we eat
may directly regulate gene expression in our bodies,” said Clay Marsh,
Director of the Center for Personalized Health Care at the Ohio State
University College of Medicine who researches microRNA expression in human
blood but who was not involved in the study.
MicroRNAs are, as the name implies, very short RNA sequences (approximately
22 nucleotides in length) discovered in the early 1990s. They are known to
modulate gene expression by binding to mRNA, often resulting in inhibition.
With the recent discovery that microRNAs circulate the blood by hitching a
ride in small membrane-encased particles known as microvesicles (see our
July 2011 feature on microvesicles, “Exosome Explosion”), there has been a
surge of interest in microRNAs as a novel class of biomarkers for a variety
of diseases.
Chen-Yu Zhang, a molecular biologist at Nanjing University in China, was
studying the role of circulating microRNAs in health and disease when he
discovered that microRNAs are present in other bodily fluids such as milk.
This gave him the “crazy idea” that exogenous microRNAs, such as those
ingested through the consumption of milk, could also be found circulating in
the serum of mammals, he recalled.
To test his hypothesis, Zhang and his team of researchers sequenced the
blood microRNAs of 31 healthy Chinese subjects and searched for the presence
of plant microRNAs. Because plant microRNAs are structurally different from
those of mammals, they react differently to oxidizing agents, and the
researchers were able to differentiate the two by treating them with sodium
periodate, which oxidizes mammal but not plant microRNAs.
To their surprise, they found about 40 types of plant microRNAs circulating
in the subjects’ blood—some of which were found in concentrations that
were comparable to major endogenous human microRNAs.
The plant microRNAs with the highest concentrations were MIR156a and MIR168a
, both of which are known to be enriched in rice and cruciferous vegetables
such as cauliflower, cabbage, and broccoli. Furthermore, the researchers
detected the two microRNAs in the blood, lungs, small intestine, and livers
of mice, in variable concentrations that significantly increased after the
mice were fed raw rice (although cooked rice was also shown to contain
intact MIR168a).
Next, the researchers scoured sequence databases for putative target genes
of MIR156a and MIR168a and found that MIR168a shared sequence
complementarity with approximately 50 mammalian genes. The most highly
conserved of these sequences across the animal kingdom was the exon 4 of the
low-density lipoprotein receptor adapter protein 1 gene (LDLRAP1).
LDLRAP1 is highly expressed in the liver, where it interacts with the low-
density lipoprotein receptor to help remove low-density lipoprotein (LDL),
aka “bad” cholesterol, from the blood.
The researchers hypothesized that MIR168a could be taken up by the
epithelial cells lining the gastrointestinal tract, packaged into
microvesicles, and secreted into the blood stream, where they can make their
way to target organs. Once in the liver, MIR168a binds to LDLRAP1 mRNA,
reducing the protein levels and ultimately impairing the removal of LDL from
the blood.
To test this hypothesis in vitro, the researchers transfected synthetic
MIR168a into a human epithelial cell line and collected the secreted
microvesicles. When they added these microvesicles to a liver cell line
called HepG2, they found that while it did not change the levels of LDLRAP1
mRNA, it did decrease the levels of the actual LDLRAP1 protein.
Likewise, the LDLRAP1 protein level decreased in the livers of live mice 3
to 7 days after eating fresh rice or being injected with synthetic MIR168a—
significantly increasing LDL in the blood. When the researchers injected the
mice with an RNA sequence that bound to and neutralized MIR168a, the
protein and LDL levels returned to normal.
“This microRNA inhibits this protein and increased the plasma LDL levels,”
Zhang said. With higher levels of circulating cholesterol, “it can
possibly increase the risk of metabolic syndrome,” he added. But more
importantly, this research points to a “new therapeutic strategy for the
treatment of diseases,” based on the enhancement or inhibition of exogenous
microRNAs.
Although the team has still a long way to go in elucidating the mechanisms
by which plant microRNAs can regulate gene expression in humans, these
initial results promise to increase the understanding of how specific
ingredients in food can mediate health and disease, Marsh said.
Indeed, Zhang suspects that this is just one example of many. With time, “I
’m confident other people will find more exogenous plant microRNAs that can
pass through the GI tract and also have effects on the host physiology,”
Zhang said.
L. Zhang, et. al., “Exogenous plant MIR168a specifically targets mammalian
LDLRAP1: evidence of cross-kingdom regulation by microRNA,” Cell Research,
doi:10.1038/cr.2011.158, 2011. | j*****d
发帖数: 787 | 2 His lab should generate transgenic plants, as soon as possible, with RNAi
cassette, targeting oncogene, and feed animal models with tumor.
they
inhibit
【在 j*****d 的大作中提到】
: http://the-scientist.com/2011/09/20/plant-rnas-found-in-mammals
: +Plant RNAs Found in Mammals
: MicroRNAs from plants accumulate in mammalian blood and tissues, where they
: can regulate gene expression.
: By Cristina Luiggi | September 20, 2011
: 11 Comments Link thisStumbleTweet thisDreamstime.com, Rewat
: WannasukMicroRNAs from common plant crops such as rice and cabbage can be
: found in the blood and tissues of humans and other plant-eating mammals,
: according to a study published today in Cell Research. One microRNA in
: particular, MIR168a, which is highly enriched in rice, was found to inhibit
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