1996-2016: Ignoring alternative splicings of pre-mRNA

By: James V. Kohl | Published on: September 29, 2017

Range of diseases may result when brain self-regulation goes awry, researchers say
There is no such thing as self-regulation of the brain. Regulation is food energy-dependent and biophysically constrained by changes in the microRNA/messenger RNA balance. The entire range of diseases is linked from the virus-driven degradation of messenger RNA to the mutations that some theorists claim may sometimes be beneficial.The theorists the make those ridiculous claims are biologically uninformed science idiots.

See for comparison: Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs. (2017)

…phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-UGU pri-miRNAs that would otherwise be poorly processed. In contrast, UGU-positive pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association.

1964: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”

The synthesis of RNA in isolated thymus nuclei is ATP dependent.

How can the fact from 1964 that ATP-dependent RNA synthesis is energy-dependent continue to be ignored? RNA synthesis is clearly linked to energy-dependent healthy longevity, which strongly suggests that the virus-driven degradation of messenger RNA has been the only obvious link to understanding the difference between normal and disease biology for more than 50 years.

Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology?

Excerpt (with my emphasis)

It is possible to detect changes in neuronal activity via the use of TC methods. TC captures a snapshot of the tissue at a moment in time, which affords the inference of neuronal activity at that time. An increase in neuronal activity can be identified either by staining for immediate early genes (IEGs), such as c-fos [24]…These methods offer insight into brain-wide information processing. An additional option that might provide a faster readout is RNA FISH. Given that mRNA transcription occurs prior to protein translation, RNA FISH could detect upregulation of IEG mRNA immediately after a behavioral experiment.

Conclusion (with my emphasis):

Emerging from the field of neuroscience, TC and optogenetics now constitute a powerful approach to the study of general biological questions and diseases by enabling the control and measurement of functional changes in living tissue [85], followed by cellular and molecular phenotyping at the whole-organ level.

The late, Robert L. Moss and colleagues linked the food energy-dependent metabolism to pheromones and the energy-dependent activation of c-fos in genes that secrete gonadotropin releasing hormone (GnRH), which is the central regulator of all vertebrate physiology and behavior.
See: Induction of FOS immunoreactivity in central accessory olfactory structures of the female rat following exposure to conspecific males (1992)
See also: Influence of male rats on the luteinizing hormone-releasing hormone neuronal system in female rats: role of the vomeronasal organ (1993)
By 1991, the link from the hypothalamic secretion of GnRH to human behavior already was almost perfectly clear.
See: Gonadotropin releasing hormone and human sexual behavior in Neuropeptides and Psychiatric Disorders (1991)

The universality of the GnRH-induced behavioral response in the nonhuman species (from lizard to monkey) and the endocrine-pituitary actions of GnRH in pituitary secretion of LH and FSH, couples with the possible relationship between human sexual behavior deficits and gonadotropin dysfunction, provided good justification to proceed with further investigation into the behavioral effects of GnRH on human sexual behavior. (p. 61)

During the next two and a half decades, pseudoscientists (e.g., social scientists) and most theorists (i.e., biologically uninformed science idiots) ignored the facts that linked the epigenetic effects of mammalian pheromones from c-fos activation from GnRH secretion to the secretion of other hormones that affect behavior in all vertebrates and invertebrates. Despite repeated advice to learn to differentiate between “effects” and “affects,” the pseudoscientists and theorists remained horribly confused.
For comparison, see the attempt to clarify cause and effect in: Correction for McEwen, Brain on stress: How the social environment gets under the skin (January, 2013)

The authors note that on page 17184, right column, first paragraph, line 4, “effect” should instead appear as “affect.”

See also: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors (2012)

2‘Effect(s)’ and ‘affect(s)’. In context, sensory input effects hormones that affect behavior. An effect of sensory input on hormones can result in behavioral affects/affects on behavior.

See also this refutation of every aspect of neo-Darwinian evolutionary theory:

Nutrient-dependent/pheromone-controlled adaptive evolution: a model (June 2013)


…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

Alternative splicings of pre-mRNA are the obvious link from natural selection for energy-dependent codon optimality and the physiology of pheromone controlled reproduction in species from microbes to humans. That fact was established in the context of this 1996 Hormones and Behavior review:
From Fertilization to Adult Sexual Behavior (1996)
See our section on molecular epigenetics (with my emphasis)

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.

Human sex differences were subsequently linked from the general principles of alternative splicing to sex differences in sexual orientation and sex differences in diseases. See 2006: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences
See also: 2009 Alternative splicing and disease

1. General principles of alternative splicing

1.1. Alternative pre-mRNA splicing regulates the function of the majority of protein-coding genes

The pre-mRNAs are now typically called microRNAs by serious scientists. It does not matter what pseudoscientists call them.  Food energy-dependent changes in the microRNA/messenger RNA balance have been linked from the information we provided about RNA-mediated cell type differentiation in our review to pheromone-controlled biophysically constrained viral latency in all living genera.
The virus-driven theft of quantized energy as information links stress from constraint-breaking mutations to all pathology. For comparison to what was known about pre-mRNA in 1996, a PubMed search for “microRNA” turns up more than 65,000 citations. The links from pre-mRNAs / microRNAs to healthy longevity or to virus-driven pathology are known to all serious scientists. Pseudoscientists are still touting their nonsense about de novo copy number variants and they keep trying to link mutations from genomic instabilities to evolution.
An Organismal CNV Mutator Phenotype Restricted to Early Human Development

De novo copy number variants (dnCNVs) arising at multiple loci in a personal genome have usually been considered to reflect cancer somatic genomic instabilities

Reported as: Copy Number Variation may be More Common Than we Thought 3/3/17 by LabRoots so-called science journalist Carmen Leitch.

Mutations don’t only involve differences in one or two bees or nucleotides, the individual letters that create the genome, some involve the replication of whole genes or portions of genes. Those mutations are called copy number variants, animated in the following video.

Does any intelligent serious scientist use the term bees and nucleotides interchangeably? Energy-dependent changes in base pairs must be linked to copy number variants and the number of variants is biophysically constrained by the physiology of pheromone-controlled reproduction in all living genera.
Simply put, food energy-dependent changes in base pairs link microRNAs to alternative splicings and from copy number variants to healthy longevity in all living genera.
See: Energy as information and constrained endogenous RNA interference At the time of my 2/15/17 recording for the Labroots virtual conference on Precision Medicine, the term microRNA had been used in 58,000 indexed works. The increase in use to more than 65,000, reflects how quickly serious scientists are making progress (at a rate of ~1000 new publications each month) Unfortunately, the link from energy-dependent microRNAs to alternative splicing has still been relatively ignored.
See also: microRNA alternative splicing 
See for additional historical perspective:  The connection between splicing and cancer (2006)

Alternative splicing is a crucial mechanism for generating protein diversity. Different splice variants of a given protein can display different and even antagonistic biological functions. Therefore, appropriate control of their synthesis is required to assure the complex orchestration of cellular processes within multicellular organisms. Mutations in cis-acting splicing elements or changes in the activity of constitutive or alternative splicing could have a profound regulatory proteins that compromise the accuracy of either impact on human pathogenesis, in particular in tumor development and progression. Mutations in splicing elements, for example, have been found in genes such as LKB1, KIT, CDH17, KLF6 and BRCA1, and changes in trans-acting regulators can affect the expression of genes such as Ron, RAC1 and CD44.

The fact that all serious scientists have known about the link from energy-dependent base pair changes and alternative splicings of pre-mRNAs/microRNAs to all biophysically constrained pheromone-controlled biodiversity via the physiology of reproduction has been ignored by pseudoscientists. The pseudoscientists make claims about protein diversity, but they rarely make claims that include the fact that all protein diversity is biophysically constrained by the availability of food energy and the pheromone-controlled physiology of reproduction in species from microbes to humans.

See for comparison:  2017 The Functional Impact of Alternative Splicing in Cancer

We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers).
Reported as: Can alternative splicing lead to cancer?
See also:  Alternative splicing, an important mechanism for cancer
Complete structure of mitochondrial respiratory supercomplex decoded by John Hewitt with this comment to his FB page:

SARCASM ALERT: Do you think this may be important to our understanding of how energy-dependent changes are linked from atoms to ecosystems and biophysically constrained by the epigenetic effects of food odors and pheromones on RNA-mediated cell type differentiation that protects all organized genomes from the virus-driven degradation of messenger RNA, which has been linked from mutations to all pathology?

Here’s why I asked: Investigating biomolecular recognition at the cell surface using atomic force microscopy (2014)

The fission yeast pheromone receptor is a kind of G protein-coupled receptor (GPCR), a typical membrane receptor protein oncell surface. These receptors are activated by pheromone binding and then enable cellular signal transduction (Kohl et al., 2001).

See also: Hanbury Brown and Twiss interferometry of single phonons from an optomechanical resonator

Reliably generating non-classical states of their motion is of interest both for addressing fundamental questions about macroscopic quantum phenomena as well as for developing quantum technologies in the domains of sensing and transduction.

Sensing and signal transduction link quantum mechanics to classical physics in the context of quantized energy as information that must be linked from the physiology of pheromone-controlled reproduction to all biodiversity and to quantum souls.
Reported as: A way to measure and control phonons
…individual phonons moving in a crystal follow the laws of quantum mechanics as opposed to classical physics.
See also Secreting and Sensing the Same Molecule Allows Cells to Achieve Versatile Social Behaviors


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