Virus-perturbed alternative splicings

By: James V. Kohl | Published on: January 22, 2016

Computing in mammalian cells with nucleic acid strand exchange
Abstract excerpt:

…we established that functional siRNA could be activated through strand exchange, and used native mRNA as programmable scaffolds for co-localizing gates and visualizing their operation with subcellular resolution.

Reported as:

Scientists Demonstrate Basics of Nucleic Acid Computing Inside Cells

Excerpt:

Cells, of course, already know how to sense toxic molecules and the development malignant tendencies, and to then take action. But those safeguards can be turned off by viruses or cancer cells that know how to circumvent natural cellular processes.

My comment: They seem unwilling to tell others how the proliferation of viruses links nutrient energy theft from viral microRNAs in cancer cells to all RNA-mediated cell type pathology.  Perhaps it is just the reporting of their research that leaves out the most important aspect of top-down causation. The anti-entropic epigenetic effect of UV light links hydrogen-atom transfer in DNA base pairs to healthy longevity or virus-driven genomic entropy in all living genera.
Other works from this group attest to that fact.
2013 Conditionally fluorescent molecular probes for detecting single base changes in double-stranded DNA
2014 MicroRNA-Based Single-Gene Circuits Buffer Protein Synthesis Rates against Perturbations
2015 Learning the Sequence Determinants of Alternative Splicing from Millions of Random Sequences
See also:  1996 From Fertilization to Adult Sexual Behavior
Excerpt: 

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…. That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
A potential ramification of epigenetic imprinting and alternative splicing may be occurring in Xq28, a chromosomal region implicated in homosexual orientation… Xq28, therefore, is a chromosomal region that has many of the heterochromatic and telomeric characteristics that participate in sexual determination and behavior in other species.

My comment: Epigenetically-effected RNA-mediated cell type differentiation has since been linked from soil bacteria and grasses to the reproductive physiology and behavior of mammals via nutrient-dependent microRNAs.
See: The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression
See also: Soma-to-Germline Transmission of RNA in Mice Xenografted with Human Tumour Cells: Possible Transport by Exosomes
See also the comment on this article by Abhay Sharma

Cossetti et al. provide experimental evidence supporting a role of exosomal RNA mediated soma to germline information transfer in transgenerational epigenetic inheritance. Notably, it is consistent with the previous bioinformatic evidence and theoretical prediction. First, analysis of genome level expression profiling data recently suggested that circulating and exosomal miRNAs may potentially mediate this transfer (1). Next, similar evidence for exosomal mRNAs and proteins was also provided (2). Later on, inheritance of behavioral effects of traumatic stress in mouse was found to accompany upregulation of an miRNA, miRNA-375, in hippocampus, serum and sperm of the exposed animals (3). Experimental designs to test a hypothetical role of exosome borne miRNAs in intercellular communication in epigenetic inheritance have also been proposed recently (4). In conclusion, prior evidence supports Cossetti et al.’s findings.
1. Sharma A. Novel transcriptome data analysis implicates circulating microRNAs in epigenetic inheritance in mammals. Gene 538:366-372 (2014).
2. Sharma A. Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritance. J. Theor. Biol. 357:143-149 (2014).
3. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat. Neurosci. 17:667-669 (2014).
4. Smythies J, Edelstein L, Ramachandran V. Molecular mechanisms for the inheritance of acquired characteristics-exosomes, microRNA shuttling, fear and stress: Lamarck resurrected? Front. Genet. 5:133 (2014).
 


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