Temperature-controlled RNA-mediated splicing efficiency

By: James V. Kohl | Published on: September 17, 2016

Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp


Our model suggested that the change in Cirbp mRNA half-life could only partially account for the transcript up-regulation at low temperature. Indeed, the splicing efficiency (α × km/ks) of Cirbp pre-mRNA was 5.7 times higher at 33°C than at 38°C. Specifically, the fractions of spliced pre-mRNAs were 48.1% and 8.5% at 33°C and 38°C, respectively. Hence, the splicing efficiency appeared to be the strongest determinant of Cirbp mRNA expression (Supplemental Table S3).

reported as: The end justifies the means, even at the cellular level


Surprisingly, the level of pre-messenger RNAs remains constant, and only the quantity of mature RNAs depends on body temperature.

My comment: Our model suggested that splicing efficiency was the strongest determinant of biophysically constrained RNA-mediated cell type differentiation in species from yeasts to mammals.
Excerpt: (from 1996)

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.

My comment: Temperature-dependent sex determination can now be linked to conserved molecular mechanisms of energy-dependent RNA-mediated amino acid substitutions and cell type differentiation in all cell types of all individuals of all living genera. That helps to explain why some researchers report their findings in a section head such as Mild cold exposure increases the expression of a single Cirbp mRNA isoform without affecting its pre-mRNA levels. If they linked the mRNA isoforms to cell type differentiation without mention of amino acids, the change of terminology confuses anyone who might otherwise recognize the fact that they were surprised to find what we detailed 20 years ago in our section head Molecular epigenetics.

See also:

My comment: Award-winning blogger, Jon Lieff inadvertently placed the surprise about temperature-dependent alternative RNA splicing into the context of cellular intelligence.

See: Alternative RNA Splicing in Evolution


It now appears that alternative splicing is, perhaps, the most critical evolutionary factor determining the differences between human beings and other creatures.

Unfortunately, despite my comment on his representations, he continues to tout evolution as an explanation for biodiversity. He may be among those who are most surprised to learn about the energy-dependent temperature-dependent interactions among hydrogen-atom transfer in DNA base pairs in solution, microRNA flanking sequences, and RNA-mediated amino acid substitutions. 

My comment: 

In our 1996 Hormones and Behavior 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.”


The alternative splicings are nutrient-dependent and appear to be enabled by the experience-dependent de novo creation of olfactory receptor genes, which enable additional receptor-mediated nutrient uptake and the metabolism of nutrients to species-specific blends of pheromones that control reproduction in species from microbes to man.

Your focus on the importance of pre-mRNA and alternative splicing is exemplary, especially in the context of neuronal plasticity.

C. elegans is the model organism of neurogenic niche construction that links nutrient-dependent ecological and pheromone-controlled social niche construction to socio-cognitive niche construction in vertebrates and invertebrates. See for review:


What you are helping to detail is self-assembly with evidence of olfactory/pheromonal self-organization that is currently missing from evolutionary theory, which attributes speciation to mutation-initiated natural selection even though there is no experimental evidence for that (as I mentioned elsewhere).

His reply:

On 10/27/13 Jon Lieff wrote:
I very much appreciate your comments on pheromone communication and its rapid and critical link to the olfactory brain. I look forward to any current references and future work to help understand the immune brain connection as well as communication in general.

My comment: So far as I know, Jon Lieff has not responded to any other posts to his blog site that I have used in attempts to get him to acknowledge what is currently known about cellular intelligence by providing current references.

See also:

Evolution (452427)

Ecological adaptation (4)

See for example: Comparative Analysis of Transcriptomes among Bombyx mori Strains and Sexes Reveals the Genes Regulating Melanic Morph and the Related Phenotypes

No experimental evidence of biologically-based cause and effect has ever suggested that interactions among transcriptoms “evolve.” Theorists and journalists/bloggers might still claim that thermodynamic cycles of protein biosynthesis and degradation “evolved” to link food odors and pheromones to all biodiversity in species from microbes to humans. But, who on Earth will believe them?

See also:

 Two fatty acyl reductases involved in moth pheromone biosynthesis

Role of olfaction in Octopus vulgaris reproduction

The Ancient Origins of Consciousness: How the Brain Created Experience

If the citation to Kohl (2013) in these three published works (above) does not convince you that energy-dependent RNA-mediated amino acid substitutions are the key to all biodiversity, see these pubmed searches. On 9/17/16, they showed the importance of word usage in the context of codon usage and energy-dependent codon optimality.

amino acid” (701715)

Isoform (173365)

isoform & amino acid (30048)

microRNA (53769)

Changes in the energy-dependent microRNA/messenger RNA balance link the sun’s anti-entropic virucidal energy to hydrogen-atom transfer in DNA base pairs in solution. Energy-dependent changes in base pairs link microRNA flanking sequences from the innate immune system to pre-mRNAs and supercoiled DNA, which protects all organized genomes from virus-drive theft of quantized energy.  Virus-driven energy theft is the link from mutations to all pathology. Nutrient-dependent biophysically constrained cell type differentiation in the context of the physiology of reproduction is the key to all healthy longevity.

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