Four microRNAs identified as playing key roles in cholesterol, lipid metabolism

October 26, 2015, Massachusetts General Hospital

Four tiny segments of RNA appear to play critical roles in controlling cholesterol and triglyceride metabolism. In their report receiving advance online publication in Nature Medicine, a Massachusetts General Hospital (MGH)-based research team describes finding how these microRNAs could reduce the expression of proteins playing key roles in the generation of beneficial HDL cholesterol, the disposal of artery-clogging LDL cholesterol, control of triglyceride levels and other risk factors of cardiovascular disease.

"While we and others have recently identified microRNAs that cholesterol and fat metabolism and trafficking, no studies to date have systematically looked at all non-coding factors - such as microRNAs - in genetic studies of human diseases and other traits," says Anders Näär, PhD, of the MGH Center for Cancer Research, corresponding author of the current study. "Using human genetic data from almost 190,000 individuals, we have linked 69 microRNAs to increased genetic risk for abnormal cholesterol and , and showed that four of these act to control proteins we know are involved in those metabolic activities."

Less than 2 percent of human DNA represents genes that code for the production of proteins. While it was originally hypothesized that the other 98 percent had no function - leading to the term "junk DNA" - it has now become apparent that these DNA sequences play essential roles in determining how, when and where protein-coding DNA is expressed. One such control mechanism is through single-stranded microRNAs, which block the expression of protein-coding genes by binding to messenger RNAs and preventing their translation into protein. In previous studies, Näär and his colleagues found that a microRNA called miR-33 suppresses production of beneficial HDL cholesterol and that antisense blocking of miR-33 increased HDL levels in an animal model.

The current study began with analysis of genome-wide association studies involving more than 188,000 individuals, which identified 69 microRNAs located near gene variants previously associated with lipid abnormalities. Using a tool that predicts the targets of microRNAs based on matches between their nucleotide sequences and those of protein-coding genes and a database of identified gene functions, the researchers arrived on four microRNAs that appear to control genes involved in cholesterol and triglyceride levels and in other metabolic functions, such as glucose metabolism. Two of these - miR-128-1 and miR-148a - were found to control the expression of proteins essential to the regulation of /lipid levels in cells and in animal models; miR-128-1 was also found to regulate fatty liver deposits, insulin signaling and maintenance of blood sugar levels.

"We are following up these findings with studies to address whether antisense blocking of these microRNAs could decrease atherosclerosis, cardiovascular disease and inflammatory fatty liver diseases in animals," says Näär, a professor of Cell Biology at Harvard Medical School and an MGH research scholar. "We hope these findings will lead to new, more effective ways of treating or even preventing and other metabolic disorders."

Explore further: Tiny antisense molecules increase 'good cholesterol' levels in obese primates

More information: Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis, DOI: 10.1038/nm.3980

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1 / 5 (2) Oct 27, 2015
Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

'This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity..."
Captain Stumpy
5 / 5 (1) Oct 27, 2015
Nutrient-dependent pheromone-controlled
and again, in refute:
"Criticisms of the nutrient-dependent pheromone-controlled evolutionary model", A. Jones, BA

from the senior staff of the mag
hello harold,
So say what's hot in the paper ... kohl. or you will have to remove it, or you pubie every forum against: it is also a way to dismantle the pseudo science. j bises
conclusion from the critique
Based on his writings, both published and unpublished, James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others' research. It was a mistake to let such a sloppy review through to be published.
1 / 5 (2) Oct 27, 2015
from the senior staff of the mag

From the editor:
The 2013 review article by James Vaughn Kohl published in Socioaffective Neuroscience & Psychology and criticized in the above Letter to the Editor was subjected to standard peer review and the revised version was accepted by me after it had been accepted by both reviewers.

Note also: Pardis Sabeti is a co-author of "Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis" and senior author of Grossman et al (2013), which I cited in my 2013 review of RNA-mediated cell type diferentiation.

Excerpt: "Two additional recent reports link substitution of the amino acid alanine for the amino acid valine (Grossman et al., 2013) to nutrient-dependent pheromone-controlled adaptive evolution. The alanine substitution for valine does not appear to be under any selection pressure in mice. The cause-and-effect relationship was established in mice by comparing the..."
Captain Stumpy
5 / 5 (1) Oct 27, 2015
From the editor:
and so was the critique by Jones, BA

please also note that Jones is a degree holding professional with specialty in Biology, whereas your highest accomplishment to date is your "honorary degree" from prague which you think makes you someone special (it doesn't. it is like getting the key to the city- it isn't a real key, nor does it open anything. it is a symbolic gesture to someone for any multitude of reasons, and can even be done in the spirit of sarcasm, satire or maliciousness)

i will always side with the evidence over your religion, kohl
especially considering your historical self-promoting narcissism which you think people should bow to
1 / 5 (2) Oct 27, 2015
Jones is a biologically uninformed science idiot who knows nothing about cell type differentiation, and who probably will work flipping burgers for the rest of his life.

See for comparison: Learning the Sequence Determinants of Alternative Splicing from Millions of Random Sequences http://www.cell.c...901271-4

In our 1996 review we wrote: Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes."
5 / 5 (2) Oct 27, 2015
Actually, as we speak, I'm sitting here running the natural sciences lab at one of my local community colleges. Kohl likes to imply I'm still at the job I had in high school many years ago.
1 / 5 (2) Oct 27, 2015
Congratulations! You have clearly shown that a biologically uninformed science idiot can go far among other biologically uninformed science idiots or among those he can help teach to become biologically uninformed science idiots.

Reminder to login tomorrow for the webinar The Hidden Effects of Epigenetic Discoveries which begins Oct 28, 2015 11:00 AM PDT.

1 / 5 (2) Oct 28, 2015
The webinar is now available on demand.

It takes less than one hour to become biologically informed and better enabled to help serious scientists move forward by abandoning the pseudoscientific nonsense about mutations and evolution that people like Andrew Jones, are still teaching others to believe in.

Keep in mind that you may already be at least 20 years behind others who have learned to link atoms to ecosystems via nutrient-dependent RNA-mediated amino acid substitutions that are fixed in the organized genomes of all living genera via the physiology of reproduction.

But now, you, too, can help to prevent the suffering and death of your loved ones, by helping them learn how to prevent virus-driven genomic entropy that they may have been taught to believe led from mutations to evolution because they were taught to believe in ridiculous theories by biologically uninformed science idiots.
Captain Stumpy
5 / 5 (1) Oct 28, 2015
But now, you, too, can help to prevent the suffering and death of your loved ones
threatening people with fear based religious proclamations that are only true in your own mind and do not reflect modern science or medicine is not only trolling, but the mark of fanatical radical religious acolytes


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