“Junk RNA” helps regulate metabolism

_{Denyse O'Leary

May 8, 2014

'Junk DNA', News}

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Further to the junk DNA guy not doing “politeness” any more when defending his challenged view that most DNA is junk, here is some RNA for him to get started on. This just in:

Regulation of metabolism by long, non-coding RNAs

… The regulation of metabolism and glucose homeostasis is orchestrated and fine-tuned by a complex interplay of tissues/organs. Currently, we are faced with an unprecedented rise of obesity in the civilized world and the concurrent increase in obesity-associated diseases such as insulin resistance and type 2 diabetes mellitus (T2D). Key to the understanding of whole-body metabolism are the pleiotropic effects of the anabolic master regulator insulin which simultaneously controls peripheral as well as central-nervous system-related aspects of metabolism (Kahn et al., 2006). Resistance toward the effects of insulin constitutes a key step in the development of metabolic disease. The exciting observation that insulin and insulin-like growth factor (IGF) 1 signaling also triggers distinct changes in lncRNA expression [e.g., of the lncRNA CRNDE (Ellis et al., 2013)] points to the fact that lncRNAs may also be implicated in the metabolic effects of insulin and the development of insulin resistance. Thus, a strong interest lies within the identification of lncRNA-mediated mechanisms governing energy and glucose homeostasis at the cell-intrinsic, organ and whole-body level. …

Non-paywalled and gets better. So don’t send non-coding RNA out with the recycling.

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VG: Here's this from a Science Daily blurb: But this work was conducted in the simplified milieu of a test tube. "These unnatural base pairs have worked beautifully in vitro, but the big challenge has been to get them working in the much more complex environment of a living cell," said Denis A. Malyshev, a member of the Romesberg laboratory who was lead author of the new report. . . . . The greatest hurdle may be reassuring to those who fear the uncontrolled release of a new life form: the molecular building blocks for d5SICS and dNaM are not naturally in cells. Thus, to get the E. coli to replicate the DNA containing these unnatural bases, the researchers had to supply the molecular building blocks artificially, by adding them to the fluid solution outside the cell. Then, to get the building blocks, known as nucleoside triphosphates, into the cells, they had to find special triphosphate transporter molecules that would do the job. What they did demonstrates that intelligent agents can cause living organisms to act in ways that are foreign to their nature. I would also add: what does this say about OOL? Not only did the needed molecules need to be there, but special "triphospate transporter molecules" had to be place in the cell membrane. How, exactly, did "random forces" bring all of this about to form the FIRST bacteria? Heaven only knows.PaV_{May 8, 2014
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And as pointed out yesterday, the first Genetic code had to be at least as complex as to current one since ‘Shannon channel capacity’ prohibits the changing of a code once it is in place:
“Because of Shannon channel capacity that previous (first) codon alphabet had to be at least as complex as the current codon alphabet (DNA code), otherwise transferring the information from the simpler alphabet into the current alphabet would have been mathematically impossible” Donald E. Johnson – Bioinformatics: The Information in Life Shannon Information – Channel Capacity – Perry Marshall http://www.metacafe.com/watch/5457552/
Yet, the genetic code, despite its inability to evolve more complexity once it is in place, is found to be optimal:
Biophysicist Hubert Yockey determined that natural selection would have to explore 1.40 x 10^70 different genetic codes to discover the optimal universal genetic code that is found in nature. The maximum amount of time available for it to originate is 6.3 x 10^15 seconds. Natural selection would have to evaluate roughly 10^55 codes per second to find the one that is optimal. Put simply, natural selection lacks the time necessary to find the optimal universal genetic code we find in nature. (Fazale Rana, -The Cell’s Design – 2008 – page 177) “The genetic code’s error-minimization properties are far more dramatic than these (one in a million) results indicate. When the researchers calculated the error-minimization capacity of the one million randomly generated genetic codes, they discovered that the error-minimization values formed a distribution. Researchers estimate the existence of 10^18 possible genetic codes possessing the same type and degree of redundancy as the universal genetic code. All of these codes fall within the error-minimization distribution. This means of 10^18 codes few, if any have an error-minimization capacity that approaches the code found universally throughout nature.” Fazale Rana – From page 175; ‘The Cell’s Design’
Even Dawkins agrees that it is impossible to change a code once it is in place
Venter vs. Dawkins on the Tree of Life – and Another Dawkins Whopper – March 2011 Excerpt:,,, But first, let’s look at the reason Dawkins gives for why the code must be universal: “The reason is interesting. Any mutation in the genetic code itself (as opposed to mutations in the genes that it encodes) would have an instantly catastrophic effect, not just in one place but throughout the whole organism. If any word in the 64-word dictionary changed its meaning, so that it came to specify a different amino acid, just about every protein in the body would instantaneously change, probably in many places along its length. Unlike an ordinary mutation…this would spell disaster.” (2009, p. 409-10) OK. Keep Dawkins’ claim of universality in mind, along with his argument for why the code must be universal, and then go here (linked site listing 23 variants of the genetic code). Simple counting question: does “one or two” equal 23? That’s the number of known variant genetic codes compiled by the National Center for Biotechnology Information. By any measure, Dawkins is off by an order of magnitude, times a factor of two. http://www.evolutionnews.org/2011/03/venter_vs_dawkins_on_the_tree_044681.html
As an aside, alternative splicing codes are found to be ‘species specific’, which, since changing of a code once it is in place is 'catastrophic', means humans and chimps have had two different origins for their 'species specific' alternative splicing code:
Evolution by Splicing – Comparing gene transcripts from different species reveals surprising splicing diversity. – Ruth Williams – December 20, 2012 Excerpt: A major question in vertebrate evolutionary biology is “how do physical and behavioral differences arise if we have a very similar set of genes to that of the mouse, chicken, or frog?”,,, A commonly discussed mechanism was variable levels of gene expression, but both Blencowe and Chris Burge,,, found that gene expression is relatively conserved among species. On the other hand, the papers show that most alternative splicing events differ widely between even closely related species. “The alternative splicing patterns are very different even between humans and chimpanzees,” said Blencowe.,,, http://www.the-scientist.com/?articles.view%2FarticleNo%2F33782%2Ftitle%2FEvolution-by-Splicing%2F Deciphering the splicing code – May 2010 Excerpt: Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences.,,, http://www.ecs.umass.edu/~mettu/ece597m/lectures/hts-papers/barash-splicing-code.pdf Breakthrough: Second Genetic Code Revealed – May 2010 Excerpt: The paper is a triumph of information science that sounds reminiscent of the days of the World War II codebreakers. Their methods included algebra, geometry, probability theory, vector calculus, information theory, code optimization, and other advanced methods. One thing they had no need of was evolutionary theory,,, http://crev.info/content/breakthrough_second_genetic_code_revealed
bornagain77_{May 8, 2014
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Vunder, here is the entire article:
Breakthrough in Artificial Genetic Code Could Lead to Custom Drugs By Carl Engelking | May 7, 2014 Excerpt: Way back in Biology 101, we learned that DNA is encoded through the nucleotide pairings of adenine to thymine and cytosine to guanine. Since the earliest days of life on Earth, these four chemicals — and only these four chemicals — have made up the DNA of every one of the myriad organisms that inhabit this planet. But what if you could expand that alphabet? As it turns out, you can. In a paper published today in Nature, scientists report that they’ve successfully introduced an entirely new base pair into the genetic structure of the bacterium E. coli. That makes the bacterium the first semi-synthetic organism carrying an expanded genetic alphabet. And just as one can create new words with new letters in the alphabet, a synthetic base pair opens up possibilities for custom-built proteins as novel drugs, vaccines and antibiotics. Creating the Base Pair In 2012, Floyd Romesberg and colleagues reported that synthetic base pairs could be successfully replicated as part of purified DNA in the lab. Translating this result into a cell was the crucial next step, but its success was far from guaranteed. In the present study, the team engineered a special E. coli strain which had the new synthetic base pairs spliced into its DNA, as well as a transporter protein that pumped the new molecules into the cell. When they placed the bacteria into a dish full of synthetic nucleotides, the cells snatched up the molecules as they replicated — fully incorporating the synthetic material into their offsprings’ genetic structure. When the synthetic molecules were removed from the environment, the natural processes of the cell eliminated the synthetic molecules from its DNA and the E. coli returned to its natural state. http://blogs.discovermagazine.com/d-brief/2014/05/07/breakthrough-in-artificial-genetic-code-could-lead-to-custom-drugs/#.U2ungFduqCd
This is all pretty much pie in the sky speculation. The supposed 'expanded genetic code' was not mapped to the production of amino acids for proteins, and thus their claim that it represents an expansion of the genetic code is 'not even wrong'. Moreover, the speculation that this could lead to the production of 'custom-built proteins as novel drugs, vaccines and antibiotics' is nothing but pure fantasy! Even using the existing code, much less a foreign code, extreme effort goes into finding proteins that are not even as good as those already found in life:
Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for the Creator - Fazale Rana Excerpt of Review: ‘Another interesting section of Creating Life in the Lab is one on artificial enzymes. Biological enzymes catalyze chemical reactions, often increasing the spontaneous reaction rate by a billion times or more. Scientists have set out to produce artificial enzymes that catalyze chemical reactions not used in biological organisms. Comparing the structure of biological enzymes, scientists used super-computers to calculate the sequences of amino acids in their enzymes that might catalyze the reaction they were interested in. After testing dozens of candidates,, the best ones were chosen and subjected to “in vitro evolution,” which increased the reaction rate up to 200-fold. Despite all this “intelligent design,” the artificial enzymes were 10,000 to 1,000,000,000 times less efficient than their biological counterparts. Dr. Rana asks the question, “is it reasonable to think that undirected evolutionary processes routinely accomplished this task?” http://www.amazon.com/gp/product/0801072093 Dr. Fuz Rana, at the 41:30 minute mark of the following video, speaks on the tremendous effort that went into building the preceding protein: Science - Fuz Rana - Unbelievable? Conference 2013 - video http://www.youtube.com/watch?v=-u34VJ8J5_c&list=PLS5E_VeVNzAstcmbIlygiEFir3tQtlWxx&index=8 Viral-Binding Protein Design Makes the Case for Intelligent Design! - Fazale Rana - June 2011 Excerpt: When considering this study, it is remarkable to note how much effort it took to design a protein that binds to a specific location on the hemagglutinin molecule. As biochemists Bryan Der and Brian Kuhlman point out while commenting on this work, the design of these proteins required: "...cutting-edge software developed by ~20 groups worldwide and 100,000 hours of highly parallel computing time. It also involved using a technique known as yeast display to screen candidate proteins and select those with high binding affinities, as well as x-ray crystallography to validate designs.2" If it takes this much work and intellectual input to create a single protein from scratch, is it really reasonable to think that undirected evolutionary processes could accomplish this task routinely? In other words, the researchers from the University of Washington and The Scripps Institute have unwittingly provided empirical evidence that the high-precision interactions required for PPIs requires intelligent agency to arise. http://www.reasons.org/viral-binding-protein-design-makes-case-intelligent-design-sick-cool Computer-designed proteins programmed to disarm variety of flu viruses - June 1, 2012 Excerpt: The research efforts, akin to docking a space station but on a molecular level, are made possible by computers that can describe the landscapes of forces involved on the submicroscopic scale.,, These maps were used to reprogram the design to achieve a more precise interaction between the inhibitor protein and the virus molecule. It also enabled the scientists, they said, "to leapfrog over bottlenecks" to improve the activity of the binder. http://phys.org/news/2012-06-computer-designed-proteins-variety-flu-viruses.html
bornagain77_{May 8, 2014
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Interesting find, VunderGuy. the scientists said they created two additions to the normal genetic code, and then prompted bacteria to incorporate these pieces of man-made DNA with few ill effects. So they intelligently designed additions to the genetic code and incorporated them? Certainly the potential for this to aid in treating diseases and expanding the boundaries of genomic medicine is there.Barb_{May 8, 2014
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Speaking of genetic material, how can ID make sense of this article here? http://www.foxnews.com/health/2014/05/08/scientists-create-organism-using-artificial-dna/VunderGuy_{May 8, 2014
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Nice Find! :)bornagain77_{May 8, 2014
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