A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status
Eukaryotic gene expression is an intricate balancing act between transcription and post-transcriptional steps of RNA metabolism. Developmental readjustment of this balance allows large cohorts of genes to be expressed in cell- and tissue-specific manner. Among other regulators, RNA-binding proteins (RBPs) provide an important means for modulating RNA processing and turnover in the context of cellular differentiation1, 2, 3, 4. For example, downregulation of the ubiquitously expressed RBP Ptbp1/PTB/hnRNAP I in the developing brain stimulates neuron-specific alternative pre-mRNA splicing patterns and stabilizes a subset of neuronal transcripts5, 6.
See also: 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… and …alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.
Please Note: ...with only a 100 amino acids the number of possible folds is an extremely large number. If 100 billion fold attempts were done each second, then the number of possibilities would be greater than the age of the universe, approximately 10 billion years.
All of the above can be placed into the context of what was reported as:
…miR-9/TTP circuitry ensures coordinated up-regulation of neuronal mRNAs in neurons and limits unscheduled accumulation of these transcripts in non-neuronal cells.
My comment: The problem for the evolution industry and the big bang cosmology industry is their attempts to portray, in theory, the conserved molecular mechanisms that link ecological variation from virus-driven changes in the microRNA/messenger RNA balance to ecological adaptations in all genera. Their ridiculous theories do not address thermodynamic cycles of protein biosynthesis and degradation, which limit the effects of virus-perturbed protein folding. The effects of viruses are limited to affects on the transgenerational epigenetic inheritance of behaviors. The behaviors must lead to successful nutrient-dependent reproduction.
The affects on epigenetically inherited behaviors invariably involve the anti-entropic effects of nutrient-dependent microRNAs that limit the accumulation of viral microRNAs, which lead to pathology. Any claim that mutations lead to the evolution of biodiversity includes the claim that the viral microRNAs that perturb protein folding can sometimes be beneficial.
The fact that nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions are so clearly involved in the link from the biophysically constrained chemistry of protein folding to cell type differentiation in all cells of all individuals of all genera makes all theorists examples of their own ignorance of physics, chemistry, and molecular epigenetics. That fact continues to manifest itself in arguments against what is known to serious scientists about RNA-mediated cell type differentiation.
Our work suggests that fine-tuning messenger stability is an important mechanism orchestrating gene expression changes during normal brain development.
My comment: The fact that protein folding stability is a finely tuned mechanism for the orchestration of gene expression attests to the role of RNA-mediated amino acid substitutions in cell type differentiation. What can be said for theories that link mutations and perturbed protein folding to the evolution of the human brain? Is there any theory that was not invented and accepted by those who have remained biologically uninformed? The ridiculous theory linked below is an example of what many pseudoscientists have accepted.
[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. Assumptions, made but not verified, were taught as fact.
For comparison, see: Combating Evolution to Fight Disease.
The evolutionary biologist Theodosius Dobzhansky famously noted that “nothing in biology makes sense except in the light of evolution,” but perhaps, too, “nothing in evolution makes sense except in the light of biology.” Although the latter might be an exaggeration, an important gap is being filled by molecular understanding of the genesis of variation that confers the ability to evolve.
My comment: The genesis of variation that confers the ability to rapidly adapt to ecological changes in the epigenetic landscape links RNA-mediated events to nutrient-dependent cell type differentiation in all genera. The cell type differentiation is perturbed by viruses that link entropic elasticity to genomic entropy in the absence of the anti-entropic energy provided by nutrients that help to ensure proper protein folding. Protein folding occurs in the context of changes in the balance of viral microRNAs and nutrient-dependent microRNAs.
See also attempt to discuss established facts in discussion of:
Each day brings more information to the attention of theorists and serious scientists, but only serious scientists respond to it and place it into the context of the experimental evidence they report, which links nutritional epigenetics to what is known about pharmacogenomics via animal models. The animal models are the basis for what has been learned about biologically-based cause and effect.
For example, see: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012).
…this could be a factory-installed safety feature across many forms of life.
My comment: Whose factory installed the RNA-mediated safety feature that enables the nutrient-dependent repair that links the biophysically constrained chemistry of protein folding via amino acid substitutions to the stability of organized genomes in all living genera?
One of my favorite “explanations” of finely-tuned systems biology that typical prevents cancer and other pathologies, comes from Carl Zimmer.
Excerpt: “Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed “the blind watchmaker.” To some extent, it just happens.”
A good explanation achieves a happy medium between too little and too much. If you assume that your reader knows as much as you do, you will be prone to leaving out crucial information. It can be hard to notice what’s missing from an explanation, because every part of it exists in your mind, if not on the page.
My comment: “…it just happens” assumes that his readers know as much as he does about RNA-mediated cell type differentiation, and that they don’t want to know anything about it — because he doesn’t.