The tipping point (revisited): 81,000 publications (1)

By: James V. Kohl | Published on: December 17, 2018

(click to enlarge)

Excerpt: miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression (2018)
Conclusion: …our results firmly establish alternative splicing as a significant predictor of organism complexity and are, in principle, consistent with an important role of transcript diversification through alternative splicing as a means of determining a genome’s functional information capacity.
Saliva of hematophagous insects: a multifaceted toolkit

…microRNAs were for the first time described in the saliva of a few blood feeding arthropods raising intriguing questions on their possible contribution to vertebrate host manipulation and pathogen transmission

Light-activated microRNA biogenesis in plants has now been linked from blood-sucking parasites to the practice of medicine outside the context of energy-dependent biophysically constrained viral latency.
For examples of other blood-sucking parasites, ask AMA members and those who support Big Pharma about the role that microRNAs play in the metabolism of food, which links the creation of enzymes to fixation of RNA-mediated amino acid substitutions and the prevention of all virus-driven pathology.
Alternatively, see: miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1 (2004)

These studies show that miR-122, a 22-nucleotide microRNA, is derived from a liver-specific noncoding polyadenylated RNA transcribed from the gene hcr. The exact sequence of miR-122 as well as the adjacent secondary structure within the hcr mRNA are conserved from mammalian species back to fish. Levels of miR-122 in the mouse liver increase to half maximal values around day 17 of embryogenesis, and reach near maximal levels of 50,000 copies per average cell before birth. Lewis et al. (2003) predicted the cationic amino acid transporter (CAT-1 or SLC7A1) as a miR-122 target. CAT-1 protein and its mRNA are expressed in all mammalian tissues but with lower levels in adult liver. Furthermore, during mouse liver development CAT-1 mRNA decreases in an almost inverse correlation with miR-122. Eight potential miR-122 target sites were predicted within the human CAT-1 mRNA, with six in the 3′-untranslated region. Using a reporter construct it was found that just three of the predicted sites, linked in a 400-nucleotide sequence from human CAT-1, acted with synergy and were sufficient to strongly inhibit protein synthesis and reduce mRNA levels. In summary, these studies followed the accumulation during development of miR-122 from its mRNA precursor, hcr, through to identification of what may be a specific mRNA target, CAT-1.

The creation of the sun’s anti-entropic virucidal energy links natural selection for food energy-dependent biophysically constrained viral latency from microRNA biogenesis and the creation of enzymes in plants to plant growth and to the food that mice and humans eat. microRNAs in the saliva of blood feeding arthropods link the viruses they carry to vector-borne diseases in humans. The metabolism of food that humans eat links feedback loops from the pheromone-controlled physiology of reproduction to healthy longevity, or it links stress to virus-driven pathology.
See also: miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression (2018)

In summary, we have provided a comprehensive analysis of the progression from miR-122 loss to gain of other microRNAs and widespread expression of low abundant mRNA transcripts in the liver. In other tissues, highly expressed microRNAs may also have evolved a dual role of target suppression and buffering of other microRNAs.

What then can be said about theorists who still tout mutations and evolution for comparison to food energy-dependent ecological adaptations.
Are they out of their minds, or living on some other planet?
Micrornas In Development And Cancer (Molecular Medicine and Medicinal Chemistry) (2011)

This book goes into detail on how microRnas represent a paradigm shift in thinking about gene regulation during development and disease, and provide the oncologist with a potentially powerful new battery of agents to diagnose and treat cancer.

See also:

microRNA: Basic Science is an ideal companion to both microRNA: Medical Evidence and microRNA: Cancer. Taken together, these three books provide a state-of-the-art overview of this rapidly-expanding and fascinating field, from the molecular level to clinical practice. It will be invaluable to medical students, physicians, and researchers, as a complete and unique guide in the exploration of microRNA in basic science, cancer and clinical practice.

microRNA: Basic Science: From Molecular Biology to Clinical Practice (Advances in Experimental Medicine and Biology) (2015)

The authors contextualize microRNAs within epigenetics and micropeptidomics, angiongenesis and atherosclerosis, endometrial pathophysiology, and more.

microRNA: Cancer: From Molecular Biology to Clinical Practice (2015)

This volume thoroughly explores of the functional role of microRNAs in cancer. It not only expertly describes the molecular mechanisms underlying the malignant transformation process but also compiles cutting-edge research on microRNAs in several forms of cancer…

microRNA: Basic Science: From Molecular Biology to Clinical Practice (Advances in Experimental Medicine and Biology) (2015)

This volume explores microRNA function in a wide array of human disorders, providing a clinical basis for precision medicine and personalized therapies using these molecules. The twenty-one chapters, all authored by internationally-renowned experts, open with an introduction contextualizing microRNA manipulation within today’s initiatives towards precision medicine.

A microRNA feedback loop regulates global microRNA abundance during aging (2018)

Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism’s life may be partially explained by a miRNA-directed mechanism of age-associated decline.

…establishes a conserved role for human NRDE2 in RNA splicing…”

The conserved role of food energy-dependent pheromone-controlled alternative splicing was predicted in 1996.
See: From Fertilization to Adult Sexual Behavior

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.

Some of the locations provide players with resources (e.g., mRNA, ATP); some with actions (e.g., convert resources, collect cards). Resources are used to build enzymes, hormones, and/or receptors, which score Health Points.

This link is to the pdf
Works by Stephen J. Bush were used in the science compilation. See for example: Correcting for Differential Transcript Coverage Reveals a Strong Relationship between Alternative Splicing and Organism Complexity

Taken together, our results firmly establish alternative splicing as a significant predictor of organism complexity and are, in principle, consistent with an important role of transcript diversification through alternative splicing as a means of determining a genome’s functional information capacity.

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The tipping point (revisited): 82,000 publications (1) | MicroRNA.pro

5 years ago

[…] a historical perspective See: The tipping point (revisited): 81,000 publications Parts 1-5 and every other “tipping point” blog post, which began on 5/16/16 with 50,000 […]

The tipping point (revisited): 81,000 publications (1)

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