" We are not only eating 'materials', we are also eating 'information '"

[Jonathan Cline]

A road to genetic self-regulation?
(That's the wetware holy grail.)
And inexpensive, too.
- "the establishment of a powerful experimental methodology to
deliver small RNAs to animals for in vivo gene silencing"


http://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2011158a.pdf


Exogenous plant MIR168a specifically targets mammalian
LDLRAP1: evidence of cross-kingdom regulation by microRNA

doi:10.1038/cr.2011.158

Received 11 August 2011; revised 23 August 2011; accepted 26 August
2011

Chen-Yu Zhang, Jiangsu Engineering Research Center for microRNA
Biology and Biotechnology, State Key Laboratory of Pharmaceutical
Biotechnology,
School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing
210093, China

Our previous studies have demonstrated that stable microRNAs (miRNAs)
in mammalian serum and plasma are
actively secreted from tissues and cells and can serve as a novel
class of biomarkers for diseases, and act as signaling
molecules in intercellular communication. Here, we report the
surprising finding that exogenous plant miRNAs are
present in the sera and tissues of various animals and that these
exogenous plant miRNAs are primarily acquired
orally, through food intake. MIR168a is abundant in rice and is one of
the most highly enriched exogenous plant
miRNAs in the sera of Chinese subjects. Functional studies in vitro
and in vivo demonstrated that MIR168a could
bind to the human/mouse low-density lipoprotein receptor adapter
protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1
expression in liver, and consequently decrease LDL removal from mouse
plasma. These findings demonstrate that exogenous
plant miRNAs in food can regulate the expression of target genes in
mammals.

Keywords: microRNA; MIR168a; LDLRAP1; low-density lipoprotein;
microvesicle; cross-kingdom

Cell Research advance online publication 20 September 2011;



News release:


We are not only eating 'materials', we are also eating 'information'

http://www.eurekalert.org/pub_releases/2011-09/aaft-wan091411.php

In a new study, Chen-Yu Zhang's group at Nanjing university present a
rather striking finding that plant miRNAs could make into the host
blood and tissues via the route of food-intake. Moreover, once inside
the host, they can elicit functions by regulating host "target" genes
and thus regulate host physiology.

MicroRNAs are a class of 19-24 nucleotide non-coding RNAs that do not
code for proteins. MicroRNAs bind to target messenger RNAs to inhibit
protein translation. In previous studies, the same group has
demonstrated that stable microRNAs (miRNAs) in mammalian serum and
plasma are actively secreted from tissues and cells and can serve as a
novel class of biomarkers for disease and act as signaling molecules
in intercellular communication.

Here, they report the surprising finding that exogenous plant miRNAs
are present in the sera and tissues of various animals and that these
exogenous plant miRNAs are primarily acquired orally, through food
intake. MIR168a is abundant in rice and is one of the most highly
enriched exogenous plant miRNAs in the sera of Chinese subjects.
Functional studies in vitro and in vivo demonstrated that MIR168a
could bind to the human/mouse low density lipoprotein receptor adapter
protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and
consequently decrease LDL removal from mouse plasma. These findings
demonstrate that exogenous plant miRNAs in food can regulate the
expression of target genes in and thus physiology of mammals.

The finding is obviously very thought-provoking; for instance, it
would indicate that in addition to eating "materials" (in the form of
carbohydrates, proteins, etc), you are also eating "information" (as
different miRNAs from distinct food sources could well bear different
consequences on the regulation of host physiology once taken by the
host due to potential regulation of different target genes as
determined by the "information" contained within the miRNA sequence),
thus providing a whole new dimension to "You are what you eat".
Furthermore, the potential significances of this finding would be:

has significantly expanded the functions of miRNAs;
is an extremely intriguing and novel idea that has far-ranging
implications for human health and metabolism;
shed new light on our understanding of cross-domain (such as animal-
plant) interactions, or perhaps even the 'co-evolution', and to open
new ways of thinking about regulation of miRNAs, and about the
potential roles of exogenous miRNAs such as those from food, plants
and insects in prey-predator interactions;
provides evidence that plant miRNAs maybe the seventh "nutrient" in
the food (the six others are: H2O, protein, FFA, carbohydrate,
vitamins and real elements);
provides a novel mechanism of development of metabolic disorder.
provides evidence that plant miRNAs may represent essential functional
molecules in Chinese traditional herb medicine,
Importantly, these results have far-reaching implications, including
the establishment of a powerful experimental methodology to deliver
small RNAs to animals for in vivo gene silencing and miRNA gain-of-
function studies. These findings also have major implications for the
genetic engineering of plants using RNAi technologies and for the
development of therapeutics that rely on small RNA delivery, since
those interested in therapeutic applications of small RNAs inject
doses of formulated or non-formulated RNAs that are up to 100mg/kg
body weight - unimaginably higher - and have difficulty seeing an
effect.

###
The researchers of this project include Lin Zhang1,*, Dongxia Hou1,*,
Xi Chen1,*, Lingyun Zhu1, Yujing Zhang1, Jing Li1, Zhen Bian1,
Xiangying Liang1, Xing Cai1, Yuan Yin1, Cheng Wang1, Tianfu Zhang1,
Dihan Zhu1, Dianmu Zhang1, Jie Xu1, Qun Chen1, Yi Ba2, Jing Liu1,
Qiang Wang1, Jianqun Chen1, Jin Wang1, Qipeng Zhang1, Junfeng
Zhang1,†, Ke Zen1,†, and Chen-Yu Zhang1,†of Jiangsu Engineering
Research Center for MicroRNA Biology and Biotechnology, State Key
Laboratory of Pharmaceutical Biotechnology, Nanjing University, 22
Hankou Road, Nanjing, Jiangsu 210093, China

This work was supported by grants from the National Natural Science
Foundation of China (no. 30225037, 30471991, 30570731), the 973
Program of China (no. 2006CB503909, 2004CB518603), the "111" Project,
the Natural Science Foundation of Jiangsu Province (no. BK2004082,
BK2006714)

Zhang et al.: " Exogenous plant MIR168a specifically targets mammalian
LDLRAP1: an evidence of cross-kingdom regulation by microRNA "
Publishing on Cell Research, September 20, 2011.

Author contact:
Chen-Yu Zhang (Jiangsu Engineering Research Center for MicroRNA
Biology and Biotechnology, State Key Laboratory of Pharmaceutical
Biotechnology, Nanjing University, China)
Tel: +86 25 8368 6234; E-mail: cyz...@nju.edu.cn

Editorial contact:
Dangsheng Li (Cell Research, Shanghai, China)
Tel: +86 21 5492 2951; E-mail: ds...@sibs.ac.cn






--
## Jonathan Cline
## jcl...@ieee.org
## Mobile: +1-805-617-0223
########################

[Nathan McCorkle]

Sent this forward to my dad just now.

---------- Forwarded message ----------
From: Nathan McCorkle <nmz...@gmail.com>
Date: Thu, Sep 22, 2011 at 9:10 PM
Subject: Fwd: " We are not only eating 'materials', we are also eating
'information '"

To: Nathan's Dad

Check this out... seems that plant micro RNA can change gene
expression in mammals, just by eating the food. Could explain
localized/native diets, things like predator/prey relationships, and
even complementary plant-plant, plant-microbe, and plant-insect
relationships.

Most drugs bind to the proteins, which are derived from and much
stronger than RNA. RNA is an intermediate message from a gene stored
in DNA, DNA is the long molecule that is kept at very high fidelity in
the cell.

If you don't allow proteins to even be created, you have complete
silencing of a genetic trait. In (my dad's) case its some protein that makes
bad cholesterol:
"All statins act by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A
HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase
pathway, the metabolic pathway responsible for the endogenous
production of cholesterol."

An enzyme is a catalytic protein, meaning it decreases the amount of
energy needed to complete a chemical reaction (think catalytic
converter in cars, helping to react the exhaust gas to be less toxic)

While (simvastatin) does a good job, the efficacy isn't 100%, some of the
protein still exists (that has function), and what's worse is that the
drug itself is hard
on your body. Silencing the RNA for such a gene would get rid of any
negative side-effects, and efficacy would be 100%

http://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2011158a.pdf

doi:10.1038/cr.2011.158

News release:

http://www.eurekalert.org/pub_releases/2011-09/aaft-wan091411.php

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--
Nathan McCorkle
Rochester Institute of Technology
College of Science, Biotechnology/Bioinformatics

--
Nathan McCorkle
Rochester Institute of Technology
College of Science, Biotechnology/Bioinformatics

[Patrik]

Reminds me of this crackpot who had a poster up at the Joint Genome
Institute's user meeting the past two years.

He was claiming horizontal gene transfer between humans and... wait
for it... coconut palms! See, in his home village in India, people
would plant coconut palms in the local cemetery. And the coconuts from
those palms would be highly prized for their flavor. Which is
apparently all you need to prove horizontal gene transfer from dead
people to coconuts and back to the humans.

I tried to point out to him that SINCE HE WAS PRESENTING THIS AT THE
JGI, it would only take half an hour or less to verify whether there
were any plant genes present IN THE HUMAN GENOME!

I also pointed out that all sort of plants live on soil containing
decaying bodies of all sorts of animals. And that literally everything
we eat contains DNA from all sorts of animals and plants. Clearly if
his hypothesis of co-evolution between coconut palms and humans in
that cemetery was correct, than this sort of horizontal gene transfer
would be going on everywhere, constantly, and we'd have all sorts of
plant-humans and human-plants walking around (not to mention worm-
humans, plant-worms, etc...)

Mind you, I pointed all this out to him *last* year. Trying to be kind
about it, because he obviously didn't understand the science behind
what he was claiming (everybody else at the poster session was either
studiously ignoring him, or laughing behind his back). Then he came
back *this* year, with essentially the same poster - sigh...



Anyway, nothing of this has ANYTHING to do with the RNA-in-food Nature
story, which seems legit and really cool!

> Tel: +86 25 8368 6234; E-mail: cyzh...@nju.edu.cn

>
> Editorial contact:
> Dangsheng Li (Cell Research, Shanghai, China)

> Tel: +86 21 5492 2951; E-mail: d...@sibs.ac.cn

[Thomas Stowe]

Perhaps not in a transgenic sense that you may be "poking at", but whether it's a hereditary intolerancy to fructose or lactose or his generations of ancestors eating the palm products passing it onto him (not the palm passing the genes from the coconut to his ancestors and him) is completely valid.

Organisms adapt to their food sources. It's easily observed in Humans, Orcas and many other organisms that aren't just single-celled or viral...

Diets are definitely heritable as well and transgenic events do take place from microorganisms and probably "food" to humans too.

http://www.nature.com/nature/journal/v467/n7317/full/nature09410.html

And as for you calling the guy a crackpot, maybe his claims were unfounded, but not entirely off base.

These aren't:

http://www.nature.com/news/2010/100407/full/news.2010.169.html

Genes from a microbe in seaweed transferred to Japanese help them process the seaweed better.

If you want, I can cite more of studies shown that will if not completely back up my assertions, they'll show that many people with expertise in these fields believe this and there's enough proof and understanding of gene transfer from our environments that it just makes sense.

Personally, I'm sure that there are RNA in foods that can activate latent genetic templates, whether that be latent "tendencies" or what have you as well, directly and overtly affecting the outcome of an individual's path from childhood to adulthood. DNA's not a static thing to only have one state from childhood to adulthood. Radiation effects alone should show you that, so why should molecular matter and genes be any different? Especially considering that our DNA isn't greatly dissimilar from a crab's. It's not like a crab or plant is made of antimatter DNA or has five helixes. DNA has gaps in the sequences in it normally, so it's not unexplainable to imagine that it happens given how many cells we have. 

Furthermore, nanostructures in our environments, air, food and water likely have a great deal of effects not many have considered as well.

This perhaps explains how damaged genetic systems passed on may influence diabetes or have created the condition in the first place. Well, that's pretty much a given with chemical intolerance and allergies being hereditary. "Eating" and what we just consider living is a form of genetic engineering and sculpting by and to "our environment".

Thomas C. Stowe

Email stowe....@gmail.com 

Texas Computer Services http://www.txpcservices.com

Portfolio/VCard/Resume/Blog http://www.thomasstowe.info

Phone +1-210-704-7289

> ## Mobile: +1-805-617-0223
> ########################

[Cathal Garvey]

Quickly, let's crowdsource prior art/"obvious to those skilled in the art" to prevent patenting of low-hanging fruit!

Replacing the gene specific regions of the studied miRNAs might yield a molecule with the same resilience to gut conditions and the same penetration properties, with different tropisms or target genes. You could use that effect for anything from transient gene knockdown to oncogene suppression to antiviral therapy to modification of food animal metabolism.

You could also ignore the miRNA business entirely and just focus on structure-forming algorithms that allow gut transit, with programmatic RNA unfolding in the cytoplasm to reveal a full reading frame.. Perhaps including reverse transcription and integration for permanent gene therapy by ingestion.

[Thomas Stowe]

Crowdsouced publication and discovery or open sourced licensing doesn't negate patenting. IP laws are crazy. Even moreso, if you've noticed the debate lately in the news you can see that there will be ruling soon that it's not going to "First to Discover." any long, but "First to File." instead. Be prepared to always have $1,000 on hand for fees for 3 12-month provisional patents.

Thomas C. Stowe

Email stowe....@gmail.com 

Texas Computer Services http://www.txpcservices.com

Portfolio/VCard/Resume/Blog http://www.thomasstowe.info

Phone +1-210-704-7289

[Cathal Garvey]

It's been first to file in most of the world for a long time. Not gonna make a huge difference to real inventors anyway if you ask me; patents are an intrument of those wealthy enough to wield them, not those clever enough to earn them.

On 23 Sep 2011 13:32, "Thomas Stowe" <stowe....@gmail.com> wrote:
> Crowdsouced publication and discovery or open sourced licensing doesn't
> negate patenting. IP laws are crazy. Even moreso, if you've noticed the
> debate lately in the news you can see that there will be ruling soon that
> it's not going to "First to Discover." any long, but "First to File."
> instead. Be prepared to always have $1,000 on hand for fees for 3 12-month
> provisional patents.
>
>
> Thomas C. Stowe
> Email stowe....@gmail.com

> <stowe....@gmail.com?subject=Thomas!-[NOT-SPAM]!>

[Kathryn H]

Very surprising, particularly since rice is cooked thoroughly before
eating.

I'm not going to forward this until it's reproduced outside China.
Their journals have a high retraction rate because researchers are
pushed to publish stuff that isn't ready for prime time, and reviewers
aren't picky. Particularly if they want to use this to back up TCM.

Extraordinary claims require extraordinary evidence. One paper isn't
enough.

Kathryn

On Sep 22, 5:11 pm, Jonathan Cline <jncl...@gmail.com> wrote:

> Tel: +86 25 8368 6234; E-mail: cyzh...@nju.edu.cn

>
> Editorial contact:
> Dangsheng Li (Cell Research, Shanghai, China)

> Tel: +86 21 5492 2951; E-mail: d...@sibs.ac.cn

[Kathryn H]

Sorry, I was reading the digest and didn't read all the newer posts.

Kathryn

[Patrick Yizhi Cai]

This claim is biased and not fair. Are you going to resequence all the genomes done by BGI as well?

Patrick

Sent from my iPad

[Jonathan Cline]

On Sep 22, 10:57 pm, Patrik <patr...@gmail.com> wrote:
>
> plant coconut palms in the local cemetery. And the coconuts from
> those palms would be highly prized for their flavor.

So, basically: "I eat dead people. Dead people's RNA"


Regarding microRNA targeting genes, it seems
characterization is again the bottleneck here.

Some of the related computational bio software is[1]:

- miRanda, using Smith-Waterman (GPL License!)
http://en.bio-soft.net/rna/miRanda.html

- RNAhybrid, for finding the minimum free energy
hybridisation of a long and a short RNA.
http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/

- MicroRNA database,
Predicted microRNA targets & target downregulation
scores. Experimentally observed expression patterns.
http://www.microrna.org

- miRBase,
searchable database of published miRNA sequences
and annotation
http://www.mirbase.org/


- Tarbase,
a manually curated collection of experimentally tested
miRNA targets, in human/mouse, fruit fly, worm, and zebrafish,
distinguishing between those that tested positive and
those that tested negative.
http://diana.cslab.ece.ntua.gr/?sec=databases


[1] See references:

- MicroRNAs: from basic science to disease biology,
Krishnarao Appasani, 2008

- The microRNA Registry. Griffiths-Jones S.
NAR 2004 32(Database Issue):D109-D111
http://nar.oxfordjournals.org/content/32/suppl_1/D109.full

- MicroRNA protocols,
Shao-Yao Ying, 2006

- 1 hr video, Science Accessible Lecture, Whitehead Member
David Bartel describes the importance of short interfering
RNAs and microRNAs.
http://whitehead.mit.edu/news/ontopic/microrna.html

- Physiological identification of human transcripts
translationally regulated by a specific microRNA,
Nakamoto M,
Hum Mol Genet. 2005 Dec 15;14(24):3813-21

[Zebedeeboy]

Sent from Samsung Mobile


Kathryn H <biola...@gmail.com> wrote:

Well you heat up your PCR primers to 96oC during PCR so I wouldn't expect a 10 min boil to kill miRNA unless it was particularly alkaline pH

Zeb

> ## Jonathan Cline
> ## jcl...@ieee.org
> ## Mobile: +1-805-617-0223
> ########################

[Cathal Garvey]

Deamination of thymidine at high temperature gradually damages dna during pcr.. Does that apply to uracil I wonder?

Still, 10 mins is small time. Really what's surprising to me is that the miRNA survives the RNAses that coat most living surfaces.

[Tom Randall]

On Sep 23, 12:55 pm, Patrick Yizhi Cai <caiyi...@gmail.com> wrote:
> This claim is biased and not fair. Are you going to resequence all the genomes done by BGI as well?
>

It is a fair statement. This finding applies to one miRNA (MIR168a) in
one species of plant, rice. It cannot be extrapolated to all or even
some other miRNA-mRNA interactions in mammals eating other vegetables
based on one study. Other such interactions would have to be tested
before this finding can be generalized. It should also be repeated by
other laboratories. Consider the following, a few years ago chronic
fatigue syndrome was linked to a virus (xenotropic murine leukemia
virus-related virus, or XMRV) by one lab which was a potentially major
breakthrough in understanding this disease. Others could not repeat
this finding and currently this relationship is in doubt. It may be
that there was some reagant contamination in that specific lab that
was causing this correlation. Anyhow, the point is that any result
like this that might have value in understanding a disease or may have
some therapeutic effect should be repeatable. If it can be, then great.

[Cathal Garvey]

Absolutely this claim requires verification. I wonder about the feasibility of sending primers and reverse transcriptase aliquots to the openPCR cohort and crowdsourcing a replication? :)

Totally not something I can arrange at present. Any volunteers for heading an effort like that? I'd happily contribute small funds.

[Tom Randall]

> genomes done by BGI as well?
>

Probably, not the sequencing but the assembly. There are so many
different programs out there for assembly, so many steps in an
assembly, and so many parameters to play with for each program, along
with custom scripts that are often used, that every group is likely
going to do the assembly differently and come up with different
answers. Then consider the different versions of the assembly programs
used. And if you do the sequencing differently, with different sized
libraries and/or technologies or sequencing machines (and different
technicians making the libraries and running the machines) the answer
will be different. And not just BGI, Wellcome, Broad, JGI and anyone
else doing it. Also consider that an assembly is usually based on one
strain or individual, assemble a different individual from the same
species and the answer will be different. Any genome assembly is just
a snapshot.

[Thomas Stowe]

I'll try and see if I can search the protocol resources I have to see if there's anything similar.

Thomas C. Stowe

Email stowe....@gmail.com 

Texas Computer Services http://www.txpcservices.com

Portfolio/VCard/Resume/Blog http://www.thomasstowe.info

Phone +1-210-704-7289

[Kathryn H]

Doesn't PCR use DNA primers? RNA is much less stable than DNA. We also
have a lot of RNAses looking to destroy foreign RNA.

Kathryn

On Sep 24, 5:09 am, Zebedeeboy <zebedee...@hotmail.com> wrote:
> Sent from Samsung Mobile
>

[Kathryn H]

The latest on XMRV Is that it was confirmed as contamination. I don't
havbattery now to look up refs (on a bus on my smartphone) but it was
in PLoS and other journals.


K

[Zebedeeboy]

I was trying to illustrate that single stranded oligonucleotides will survive boiling. RNA is not really intrinsically unstable, but as someone else pointed out is readily degraded by ribonucleases. What the situation is in boiled dried rice heaven alone knows but miRNA was orignally discovered in plants I think so I wouldn't be surprised for it to be dealt with differently from mRNA. Also if you look at the size profile of total RNA degraded by endogenous RNases there is a substantial amount of sub-50bp material present.

Zeb

Sent from Samsung Mobile

Kathryn H <biola...@gmail.com> wrote:


############

[Giovanni Lostumbo]

This suggests a DNA analogy to prion uptake, as in Kuru disease
(Creutzfeldt–Jakob disease)- instead of protein, it's microRNAs,
suggesting some diseases may be uptaken from the environment via DNA
that works in a catalytic mechanism on the DNA. An organism's or
organismless molecule that affects a host chromosome epigenetically
would be Lamarckian in phenomena.

On Sep 23, 5:00 pm, Jonathan Cline <jncl...@gmail.com> wrote:
> On Sep 22, 10:57 pm, Patrik <patr...@gmail.com> wrote:
>
>
>
> > plant coconut palms in the local cemetery. And the coconuts from
> > those palms would be highly prized for their flavor.
>
> So, basically: "I eat dead people.  Dead people's RNA"
>
> Regarding microRNA targeting genes, it seems
> characterization is again the bottleneck here.
>
> Some of the related computational bio software is[1]:
>

> - miRanda, using Smith-Waterman (GPL License!)http://en.bio-soft.net/rna/miRanda.html

>
> - RNAhybrid, for finding the minimum free energy

> hybridisation of a long and a short RNA.http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/

>
> - MicroRNA database,
> Predicted microRNA targets & target downregulation

> scores. Experimentally observed expression patterns.http://www.microrna.org

>
> - miRBase,
> searchable database of published miRNA sequences

> and annotationhttp://www.mirbase.org/

>
> - Tarbase,
> a manually curated collection of experimentally tested
> miRNA targets, in human/mouse, fruit fly, worm, and zebrafish,
> distinguishing between those that tested positive and

> those that tested negative.http://diana.cslab.ece.ntua.gr/?sec=databases

>
> [1] See references:
>
> - MicroRNAs: from basic science to disease biology,
> Krishnarao Appasani, 2008
>
> - The microRNA Registry. Griffiths-Jones S.

> NAR 2004 32(Database Issue):D109-D111http://nar.oxfordjournals.org/content/32/suppl_1/D109.full

>
> - MicroRNA protocols,
> Shao-Yao Ying, 2006
>
> - 1 hr video, Science Accessible Lecture, Whitehead Member
> David Bartel describes the importance of short interfering

> RNAs and microRNAs.http://whitehead.mit.edu/news/ontopic/microrna.html

[Kathryn H]

Well, if you work with RNA then you'd know better than I do. My
knowledge is second-hand, from colleagues who had to use nuclease-free
water in experiments, clean their work areas with anti-nuclease
solutions, and generally be very very picky that their RNA survived.

Anyhow, I mentioned XMRV = contamination but didn't have the
wherewithal to link to a reference.

Here is a blog that explains what's going on and has a link to the big
Science paper.
http://scienceblogs.com/erv/2011/09/xmrv_and_chronic_fatigue_syndr_27.php

Kathryn

On Sep 25, 5:12 am, Zebedeeboy <zebedee...@hotmail.com> wrote:
> I was trying to illustrate that single stranded oligonucleotides will survive boiling. RNA is not really intrinsically unstable, but as someone else pointed out is readily degraded by ribonucleases. What the situation is in boiled dried rice heaven alone knows but miRNA was orignally discovered in plants I think so I wouldn't be surprised for it to be dealt with differently from mRNA. Also if you look at the size profile of total RNA degraded by endogenous RNases there is a substantial amount of sub-50bp material present.
>
> Zeb
> Sent from Samsung Mobile
>

[Nathan McCorkle]

On Fri, Sep 23, 2011 at 12:46 PM, Kathryn H <biola...@gmail.com> wrote:
> Very surprising, particularly since rice is cooked thoroughly before
> eating.
>
> I'm not going to forward this until it's reproduced outside China.
> Their journals have a high retraction rate because researchers are
> pushed to publish stuff that isn't ready for prime time, and reviewers
> aren't picky. Particularly if they want to use this to back up TCM.

This wasn't published in a Chinese journal though, its in Nature...
does Nature have a high retraction rate?

>
> Extraordinary claims require extraordinary evidence. One paper isn't
> enough.

Interested to see if there are any related papers since/coming

[Alex Hoekstra]

The Zhang paper actually examined several miRNAs (MIR156a, MIR168a and MIR166a) from several plant sources, both cooked and uncooked (including rice, potatoes, wheat and bok choy).

You're absolutely right, though, in that it warrants significant further exploration before any meaningful claims could be made about the impact of one veggie or another.

To me, though, this is absolutely fascinating.  It might hold tremendous implications for synth bio and therapeutic RNAi.

[Jonathan Cline]

On Thursday, September 22, 2011 5:11:46 PM UTC-7, Jonathan Cline wrote:

A road to genetic self-regulation?

http://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2011158a.pdf


Exogenous plant MIR168a specifically targets mammalian
LDLRAP1: evidence of cross-kingdom regulation by microRNA

doi:10.1038/cr.2011.158

Received 11 August 2011; revised 23 August 2011; accepted 26 August
2011

Chen-Yu Zhang, Jiangsu Engineering Research Center for microRNA
Biology and Biotechnology, State Key Laboratory of Pharmaceutical
Biotechnology,
School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing
210093, China

Our previous studies have demonstrated that stable microRNAs (miRNAs)
in mammalian serum and plasma are
actively secreted from tissues and cells and can serve as a novel
class of biomarkers for diseases, and act as signaling
molecules in intercellular communication. Here, we report the
surprising finding that exogenous plant miRNAs are
present in the sera and tissues of various animals and that these
exogenous plant miRNAs are primarily acquired
orally, through food intake.

Monsanto has a critique of the above paper, refuting it's conclusion (and coincidentally reenforcing Monsanto's belief in it's genetically modified foods' safety):

https://www.monsanto.com/files/Pages/zhang.aspx

"""

Technical Analysis: Zhang et al.

Monsanto Company

1/10/2012

Zhang et al. (2011) demonstrate that, among the very large number of microRNAs (miRNAs) in plants, a small number can be detected in human and animal blood. In mice, the authors show that following ingestion of large doses of one particular miRNA (MIR168a), MIR168a was absorbed, was detectable in the serum and liver, protein from a particular gene (LDLRAP1) involved in the removal of LDL (“bad”) cholesterol from blood was reduced and as a result, LDL levels in the mice were increased.

The authors suggest that such a “cross-kingdom” effect – a plant gene product (MIR168a) regulating animal gene expression – may be a common phenomenon; and that miRNAs in food may regulate specific genes in animals based upon matching sequences between plant miRNAs and mammalian genes.

Since this paper was published, Monsanto scientists have thoroughly studied the work and its relevance to the safety assessment of genetically modified (GM) crops and foods derived from them. 

There is too little experimental evidence to conclude that the regulation of animal genes by plant miRNAs is an important diet-mediated phenomenon.
....

• After a careful examination of the paper, we have identified a number of relevant facts that should be taken into account when looking at data and the relevancy of the findings. 
• Of the many thousands of plant miRNAs, only a small number are found in human or animal blood.

• The absence of most plant miRNAs in serum indicates:
• Absorption may be selective;
• Only some miRNAs in foods have properties which allow them to survive in foods, the GI tract, and serum;
• Only relatively abundant miRNAs are present at high enough levels to be detected;
• Or some combination of these factors.

...

There is a broad foundation of evidence that supports the safety of GM crops that express siRNAs.  These data have been reviewed and accepted by Regulatory authorities globally.  Monsanto will continue to examine all new evidence published in the scientific literature and our own studies.  We are committed to the safety of our products and to safety of the food and feed products produced from them.

[Nathan McCorkle]

Hmm, that was underwhelming... I was excited to hear an update,  but man was that weak

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[Daniel C.]

On Sun, May 6, 2012 at 12:19 AM, Jonathan Cline <jnc...@gmail.com> wrote:
> There is a broad foundation of evidence that supports the safety of GM crops
> that express siRNAs.  These data have been reviewed and accepted by
> Regulatory authorities globally.  Monsanto will continue to examine all new
> evidence published in the scientific literature and our own studies.  We are
> committed to the safety of our products and to safety of the food and feed
> products produced from them.

While I personally believe that GM crops are perfectly safe to
consume, this response is a little too reminiscent of the tobacco
industry's response to cancer-related studies for my complete comfort.
(I'm talking about the political arena here, and how these
similarities may be noted and capitalized on by others. It doesn't
make me uncomfortable about eating GM food.)

-Dan

[Nathan McCorkle]

Dan, not sure how this connects to politics... what GMO plants use si or miRNA. All I can see is that Monsanto excels with plant genomics, and this is simply an update regarding a potentially groundbreaking discovery.

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[Daniel C.]

On Mon, May 7, 2012 at 6:24 PM, Nathan McCorkle <nmz...@gmail.com> wrote:
> Dan, not sure how this connects to politics... what GMO plants use si or
> miRNA. All I can see is that Monsanto excels with plant genomics, and this
> is simply an update regarding a potentially groundbreaking discovery.

The phrasing of their statement just reminded me of a scene from Thank
You For Smoking. I'm always worried how news about GMOs will be
taken, and the congruity between these two things made me worry a bit
more. That's all.

-Dan

[Jonathan Cline]

Follow-up article :

 (free full text)

J Nutrigenet Nutrigenomics 2013;6:16-31
(DOI:10.1159/000345826) 

The Emerging Role of MicroRNAs in the Regulation of Gene Expression by Nutrients

García-Segura L. · Pérez-Andrade M. · Miranda-Ríos J.

[Patrik D'haeseleer]

Very cool stuff!

Of course, we've known forever that what we eat affects our health, not the least of which is by affecting the microbiome that lives in our gut, and how that feeds back on our health. This is just yet another mechanism that happens to work a bit more at the direct genetic level.

Of course, the overall health impact via this mechanism may be miniscule, and there is no reason to believe that GMOs would pose any greater risk in this respect than your average novel crop variety. But this mechanism could definitely offer some very interesting novel therapeutic opportunities.

Patrik