RNA-mediated regulatory mechanisms link microbes to humans (3)

By: James V. Kohl | Published on: December 15, 2015

See also: RNA-mediated regulatory mechanisms link microbes to humans and RNA-mediated regulatory mechanisms link microbes to humans (2)

Regulation of gene expression

The effects of miRNA dysregulation of gene expression seem to be important in cancer.[10] For instance, in gastrointestinal cancers, a 2015 paper identified nine miRNAs as epigenetically altered and effective in down-regulating DNA repair enzymes.[11]
The effects of miRNA dysregulation of gene expression also seem to be important in neuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depressive disorder, Parkinson’s disease, Alzheimer’s disease and autism spectrum disorders.[12][13][14]

My comment: The epigenetic effects of nutrient-dependent microRNAs are clearly linked to prevention of DNA damage by viruses and to DNA repair in the context of the nutrient-dependent physiology of reproduction in all living genera.  Pseudoscientists have linked mutations and dysregulation of gene expression to evolution with claims that some mutations are beneficial while also ignoring the fact that RNA-mediated amino acid substitutions link energy-dependent changes in base pairs to cell type differentiation in all living genera via their biophysically constrained physiology of reproduction.
Nutrient stress and social stress alter thermodynamic cycles of protein biosynthesis and degradation that link heat shock proteins to buffered RNA-mediated cell type differentiation, but the buffers fail when overwhelmed by viruses that steal the nutrient energy from cells in the absence of proper nutrition or presence of physical and/or social stress. The heat shock response is the best indicator of how stress-related pathology arises, yet it has been largely ignored because neo-Darwinian theorists claim that mutations can be beneficial.
See for comparison to the pseudoscientific nonsense of neo-Darwinian theories:

En’Cas’ing The Stress: Engineering a Human Cell Line Knockout of Heat Shock Response Genes

Saturday, February 13, 2016
Gabriela Canales, University of Maryland, Baltimore County, Baltimore, MD
The Heat Shock Response (HSR) is an evolutionarily conserved response to high temperatures and other stresses that controls adaptive proteostasis, and is primarily regulated by the factor, Heat shock transcription factor 1 (HSF1).  In mammalian cells, HSF1 is converted from an inactive monomeric form to an active trimer in response to heat stress. A ribonucleoprotein complex comprising of eukaryotic translation elongation factor eEF1A1, and a long noncoding RNA HSR1 are the key components of HSF1 activation. Once activated, HSF1 is recruited to Heat Shock Protein (HSP) promoter regions, upregulating chaperone activity in the cell. Along with mediating initiation of HSR, eEF1A1 is also a vital component of protein synthesis machinery. Interestingly, another isoform of eEF1A, called eEF1A2, is expressed in some specialized terminally differentiated cells of skeletal muscle, heart, pancreatic islets and motor neurons, all of which are prone to protein aggregation. The two isoforms are 92% identical and are reciprocally regulated. To better understand the role of eEF1A1 and HSF1 proteins in humans, we use a CRISPR-Cas9 nickase system to knockout HSF1 and eEF1A1 in a human cell line. We showed that the hTERT-immortalized, normal diploid foreskin fibroblast cell line, BJ-5ta, produces both eEF1A isoforms. This will allow us to perform eEF1A1 knockout in these cells. We hypothesize that HSF1 knockout cell line will survive under normal conditions but express very low thermotolerance. Conjointly, we hypothesize that the elimination of eEF1A1 may be compensated by the upregulation of eEF1A2. If viable, the eEF1A1 knockout cell line will be used for screening mutants of eEF1A2 restoring activation of HSR. Both HSF1 and eEF1A1 knockout lines will also be used for future studies to improve upon the current model of the HSR pathway and potentially reveal therapeutic targets for diseases like ALS, Alzheimer’s disease, Parkinson’s disease, type 2 diabetes, and amyloidosis.

See also:

From Toxins to Culture: How Environment Shapes the Infant Brain

Sunday, February 14, 2016: 1:30 PM-4:30 PM

Prenatal and perinatal environmental factors, from toxins to maternal care and culture, profoundly influence the brains of infants, sometimes resulting in lifelong pathologies. The effects of these factors have only recently been rigorously assessed in humans, and the mechanisms by which they affect the brain are only beginning to be understood. This symposium discusses recently established links between autism and vehicular air pollution in both the developed and developing world; and how the microbiome, a target for infections and nutrition-related pathologies, directly affects the developing brain and can contribute to development of autism. The session also discusses how maternal inputs and cultures modify the impact of the physical environment on the brain, and how epigenetic mechanisms mediate the long-term impacts of prenatal and perinatal factors. These findings have broad implications for policies to preserve the health of children and adults around the world.

Beate Ritz, UCLA
Air Pollution Impacts Fetal Development and Increases Autism Risk

Elaine Y. Hsiao, University of California, Los Angeles (UCLA)
The Role of Gut Microbiomes in Neurodevelopmental Disorders

Bruce McEwen, Rockefeller University
Mother-Infant Interactions Influence Both Cognitive and Physical Development

Moshe Szyf, McGill University
Nurture Alters Nature through Epigenetic Modifications of DNA


…will present evidence that the “social environment” early in life can alter DNA methylation, the basis for the emerging field of “social epigenetics”. By highlighting the impact that external factors and the social environment can have on gene expression, he will provide a mechanistic basis for the long term effects of early childhood experience.

My comment: Watch closely as sources of science news that have banned me try to integrate everything that Bruce McEwen taught me about how to link cell type differentiation across species. I’ve done that with my model since I first met Bruce in the early 1990’s.

Others must now try to link epigenetically-effected RNA-directed DNA methylation from nurture to nature without referencing any of my published works. For example, the invited review of nutritional epigenetics I submitted also links atoms to ecosystems via RNA-mediated amino acid substitutions and cell type differentiation in all cell types of all individuals of all living genera via the effect of sensory input on gene activation and hormones that affect behavior.

See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems posted to Figshare.com on April 11, 2014

When the submission was returned without review, I realized that the guest editors of the special issue of Nutrients had “baited” me, and quickly placed the review into an open access venue before they published the series of articles that included bits and pieces of my submission.

The reason for the invited submission was prior publication of Nutrient-dependent/pheromone-controlled adaptive evolution: a model, which integrated all the works I published with or without co-authors since 1995 book publication.

If not for the fact that Anna Di Cosmo’s group cited my 2013 review, there would be no source for recognition of the links from atoms to ecosystems that I portrayed with examples across species in the context of RNA-mediated amino acid substitutions.

See: Role of olfaction in Octopus vulgaris reproduction

Excerpt (p. 61):

Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).

Happy Valentine’s Day February 14, 2016
Please watch for the articles to appear that claim there is no such thing as human pheromones between now and then. And, see also:


Notify of
Inline Feedbacks
View all comments

[…] See also: RNA-mediated regulatory mechanisms link microbes to humans (3) […]

Want more on the same topic?

Swipe/Drag Left and Right To Browse Related Posts: