how i look desperatly trying to get someone to respond to me so i can force them to listen to me talk and explain RNA and RNA editing and how many funky senarios it would lead to
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how i look desperatly trying to get someone to respond to me so i can force them to listen to me talk and explain RNA and RNA editing and how many funky senarios it would lead to
Octopus And Squid Evolution Is Officially Weirder Than We Could Have Ever Imagined
"... in April last year scientists discovered that octopuses, along with some squid and cuttlefish species, routinely edit their RNA (ribonucleic acid) sequences to adapt to their environment....that's really not how adaptations usually happen in multicellular animals. When an organism changes in some fundamental way, it typically starts with a genetic mutation - a change to the DNA. Those genetic changes are then translated into action by DNA's molecular sidekick, RNA. You can think of DNA instructions as a recipe, while RNA is the chef that orchestrates the cooking in the kitchen of each cell, producing necessary proteins that keep the whole organism going.
But RNA doesn't just blindly execute instructions - occasionally it improvises with some of the ingredients, changing which proteins are produced in the cell in a rare process called RNA editing. When such an edit happens, it can change how the proteins work, allowing the organism to fine-tune its genetic information without actually undergoing any genetic mutations. But most organisms don't really bother with this method, as it's messy and causes problems more often that solving them....
In 2015, researchers discovered that the common squid has edited more than 60 percent of RNA in its nervous system. Those edits essentially changed its brain physiology, presumably to adapt to various temperature conditions in the ocean....at least two species of octopus and one cuttlefish do the same thing on a regular basis. To draw evolutionary comparisons, they also looked at a nautilus and a gastropod slug, and found their RNA-editing prowess to be lacking.
"This shows that high levels of RNA editing is not generally a molluscan thing; it's an invention of the coleoid cephalopods,"....
The researchers analysed hundreds of thousands of RNA recording sites in these animals, who belong to the coleoid subclass of cephalopods. They found that clever RNA editing was especially common in the coleoid nervous system.....
It's true that coleoid cephalopods are exceptionally intelligent.....
So it's certainly a compelling hypothesis that octopus smarts might come from their unconventionally high reliance on RNA edits to keep the brain going.....But it's not just that these animals are adept at fixing up their RNA as needed - the team found that this ability came with a distinct evolutionary tradeoff, which sets them apart from the rest of the animal world.
In terms of run-of-the-mill genomic evolution (the one that uses genetic mutations, as mentioned above), coleoids have been evolving really, really slowly. The researchers claimed that this has been a necessary sacrifice - if you find a mechanism that helps you survive, just keep using it....in order to maintain this flexibility to edit RNA, the coleoids have had to give up the ability to evolve in the surrounding regions...
As the next step, the team will be developing genetic models of cephalopods so they can trace how and when this RNA editing kicks in. "It could be something as simple as temperature changes or as complicated as experience, a form of memory,".
Just when we thought octopuses couldn't be any weirder, it turns out that they and their cephalopod brethren evolve differently from nearly
A polip és a tintahal evolúciója hivatalosan is furcsább, mint azt valaha is gondoltuk volna
"... tavaly áprilisban a tudósok felfedezték, hogy a polipok, valamint néhány tintahal- és tintahalfaj rutinszerűen szerkesztik RNS (ribonukleinsav) szekvenciáikat, hogy alkalmazkodjanak a környezetükhöz....ez valóban nem így szokott történni az alkalmazkodás a többsejtű állatoknál. Amikor egy szervezet valamilyen alapvető módon megváltozik, az általában genetikai mutációval - a DNS megváltoztatásával - kezdődik. Ezeket a genetikai változásokat aztán a DNS molekuláris segítője, az RNS ülteti át a gyakorlatba. A DNS utasításaira úgy is gondolhatunk, mint egy receptre, míg az RNS a séf, aki az egyes sejtek konyhájában a főzést irányítja, és a szükséges fehérjéket állítja elő, amelyek az egész szervezetet működésben tartják.
Az RNS azonban nem csak vakon hajtja végre az utasításokat - időnként improvizál néhány hozzávalóval, megváltoztatva, hogy milyen fehérjék termelődnek a sejtben egy ritka folyamat során, amelyet RNS-szerkesztésnek neveznek. Amikor egy ilyen szerkesztés megtörténik, megváltoztathatja a fehérjék működését, lehetővé téve a szervezet számára, hogy finom hangolja genetikai információit anélkül, hogy ténylegesen genetikai mutáción menne keresztül. A legtöbb szervezet azonban nem igazán foglalkozik ezzel a módszerrel, mivel rendetlen és gyakrabban okoz problémát, mint megoldja őket.....
2015-ben kutatók felfedezték, hogy a közönséges tintahal az idegrendszerében található RNS több mint 60 százalékát szerkesztette. Ezek a szerkesztések lényegében megváltoztatták az agyának fiziológiáját, feltehetően azért, hogy alkalmazkodjon az óceán különböző hőmérsékleti viszonyaihoz....legalább két polipfaj és egy tintahalfaj rendszeresen csinálja ugyanezt. Az evolúciós összehasonlítás érdekében egy nautilust és egy csigát is megvizsgáltak, és megállapították, hogy az ő RNS-szerkesztési képességeik hiányoznak.
"Ez azt mutatja, hogy a magas szintű RNS-szerkesztés nem általában a puhatestűek sajátja; ez a koleoid lábasfejűek találmánya" - írja a .....
A kutatók több százezer RNS-felvételi helyet elemeztek ezekben az állatokban, amelyek a lábasfejűek koleoid alosztályába tartoznak. Azt találták, hogy az okos RNS-szerkesztés különösen gyakori volt a koleoid idegrendszerben.....
Való igaz, hogy a koleoid lábasfejűek kivételesen intelligensek.....
Tehát mindenképpen meggyőző hipotézis, hogy a polipok okossága abból eredhet, hogy az agyuk működésének fenntartása érdekében szokatlanul nagymértékben támaszkodnak az RNS-szerkesztésre.....De nem csak arról van szó, hogy ezek az állatok ügyesen javítják az RNS-üket szükség szerint - a csapat megállapította, hogy ez a képesség egy határozott evolúciós kompromisszummal járt, ami megkülönbözteti őket az állatvilág többi részétől.
A szokásos genomikus evolúciót tekintve (amely a fent említett genetikai mutációkat használja), a koleoidok nagyon-nagyon lassan fejlődtek. A kutatók azt állították, hogy ez egy szükséges áldozat volt - ha találsz egy mechanizmust, ami segít a túlélésben, csak használd tovább....mivel a rugalmasság fenntartása érdekében az RNS szerkesztéséhez a koleoidoknak le kellett mondaniuk a környező régiók evolúciós képességéről...
Következő lépésként a csapat genetikai modelleket fog kifejleszteni a fejlábúakról, hogy nyomon követhessék, hogyan és mikor lép életbe ez az RNS-szerkesztés. "Ez lehet valami olyan egyszerű, mint a hőmérséklet-változás, vagy olyan bonyolult, mint a tapasztalat, a memória egy formája".
A Genetic Oddity May Give Octopuses and Squids Their Smarts
By Steph Yin
Coleoid cephalopods, a group encompassing octopuses, squid and cuttlefish, are the most intelligent invertebrates: Octopuses can open jars, squid communicate with their own Morse code and cuttlefish start learning to identify prey when they’re just embryos.
In fact, coleoids are the only “animal lineage that has really achieved behavioral sophistication” other than vertebrates, said Joshua Rosenthal, a senior scientist at the Marine Biological Laboratory in Woods Hole, Mass. This sophistication could be related to a quirk in how their genes work, according to new research from Dr. Rosenthal and Eli Eisenberg, a biophysicist at Tel Aviv University.
Continue Reading
Squid recode their genetic make-up on-the-fly to adjust to their surroundings
The principle of adaptation—the gradual modification of a species' structures and features—is one of the pillars of evolution. While there exists ample evidence to support the slow, ongoing process that alters the genetic makeup of a species, scientists could only suspect that there were also organisms capable of transforming themselves ad hoc to adjust to changing conditions.
Now a new study published in eLife by Dr. Eli Eisenberg of Tel Aviv University's Department of Physics and Sagol School of Neuroscience, in collaboration with Dr. Joshua J. Rosenthal of the University of Puerto Rico, showcases the first example of an animal editing its own genetic makeup on-the-fly to modify most of its proteins, enabling adjustments to its immediate surroundings. The research, conducted in part by TAU graduate student Shahar Alon, explored RNA editing in the Doryteuthis pealieii squid.
"We have demonstrated that RNA editing is a major player in genetic information processing rather than an exception to the rule," said Dr. Eisenberg. "By showing that the squid's RNA-editing dramatically reshaped its entire proteome—the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time—we proved that an organism's self-editing of mRNA is a critical evolutionary and adaptive force." This demonstration, he said, may have implications for human diseases as well.
Using the genetic red pencil
RNA is a copy of the genetic code that is translated into protein. But the RNA "transcript" can be edited before being translated into protein, paving the way for different versions of proteins. Abnormal RNA editing in humans has been observed in patients with neurological diseases. The changing physiological appearance of squid and octopuses over their lifetime and across different habitats has suggested extensive recoding might occur in these species. However, this could never be confirmed, as their genomes (and those of most species) have never been sequenced.
For the purpose of the new study, the researchers extracted both DNA and RNA from squid. Harnessing DNA sequencing and computational analyses at TAU, the team compared the RNA and DNA sequences to observe differences. The sequences in which the RNA and DNA did not match up were identified as "edited."
"It was astonishing to find that 60 percent of the squid RNA transcripts were edited. The fruit fly, for the sake of comparison, is thought to edit only 3% of its makeup," said Dr. Eisenberg. "Why do squid edit to such an extent? One theory is that they have an extremely complex nervous system, exhibiting behavioral sophistication unusual for invertebrates. They may also utilize this mechanism to respond to changing temperatures and other environmental parameters."
Read more here.
Image: Inshore Longfin Squid (Credit: eclectic echoes on Flickr.)
Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites has been published on http://www.michalbrzezinski.org/blog/largest-most-accurate-list-of-rna-editing-sites/
Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites
Researchers have compiled the largest and most rigorously validated list to date of the genetic sites in fruit flies where RNA transcribed from DNA is then edited by an enzyme to affect a wide variety of fundamental biological functions. The list yielded several biological insights and can aid further research on RNA transcription because flies are a common model in that work.
http://feedproxy.google.com/~r/sciencedaily/~3/uUahvFBdzIw/130929142735.htm
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Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites has been published on http://www.michalbrzezinski.org/blog/largest-most-accurate-list-of-rna-editing-sites/
Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites
Researchers have compiled the largest and most rigorously validated list to date of the genetic sites in fruit flies where RNA transcribed from DNA is then edited by an enzyme to affect a wide variety of fundamental biological functions. The list yielded several biological insights and can aid further research on RNA transcription because flies are a common model in that work.
http://feedproxy.google.com/~r/sciencedaily/~3/uUahvFBdzIw/130929142735.htm
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Covering All Our Bases
Biology concepts – nucleoside, tRNA, RNA editing, nonstandard bases, DNA oxidation
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Specialized pieces are needed to best build special Lincoln
Log structures, like this castle. This is much like how
specialized nucleosides are needed to carry out special
functions of RNAs. Really – a log castle? Wouldn’t the
Black Knight just burn it?
Last week, we used Lincoln Logs as a model for the different nucleic acids. The small logs mean little until you put them together in an order of which you can make – a cabin, for example. This week we can take the analogy a little further.
Some editions of Lincoln Logs have specialized pieces for building special buildings. These buildings have different purposes, like a sawmill or a bank, and the specialized pieces help them carry out their function of being that building.
Low and behold, there are special building blocks for building specialized nucleic acid structures; usually these are RNAs for which the usual building blocks just won’t do. These are the exceptions to the nucleotide rules of A, C, G, and T for DNA and A C, G, and U for RNA.
There are a few different nucleotides located in DNA molecules, but to date all these have been found to be damaged bases. Oxidized guanosine bases have been the most commonly identified mutations, because guanine is more susceptible to oxidation than the other bases. However, a recent study has identified a 6-oxothymidine in the placental DNA of a smoker.
More than 20 oxidized DNA bases have been found at one time or another. Their importance lies in their inability to direct correct base pairing in a replicating DNA or a transcribed RNA. In particular, 8-oxoguanosine in a DNA molecule often base pairs with A instead of C, while an oxidized 8-oxoguanosine nucleotide (damaged before it is incorporated into a DNA) will often be put in where a T should rightfully have been placed.
Both of these problems would lead to mistakes in replication or transcription. Some of these mistakes could be in places that matter. If they change a codon, they might cause the wrong amino acid to be incorporated and the resulting protein might be nonfunctional. Or they could create or destroy a stop codon or a splice site. These would definitely alter the resulting protein. Mistakes like this spell disease or cancer.
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The top left image shows how 8-oxoguanine is produced by
oxidative damage or radiation. The bottom left shows it
effects on DNA. There can be a miscmatch base pairing
between G and A instead of G and C when the G is damaged.
One possible result is shon on the right. Huntington’s
disease may involve the mismatching of unrepaired
8-oxoguanosines with adneosines. As a result, areas of the
brain are lost and the fluid filled sinuses are enlarged.
Oxoguanosine has been the most studied of the oxidized bases, and several diseases have been linked to this mutation. Many cancers have shown this mutation – leukemias, breast cancer, colorectal cancer, etc. But in addition, things like Parkinson’s disease, Huntington’s disease, Lou Gherig’s disease (ALS), and cystic fibrosis have been correlated with 8-oxoguanosine.
Don’t make the mistake of assuming that an 8-oxoguanosine is the cause of any or all of these diseases, most have many potential causes. The point is that this mutation maycontribute to these diseases in some cases. The point then is to find out how to better prevent or repair them. However, your body is pretty good at doing this itself – if everything is behaving normally.
There are specific repair pathways dedicated to removing and replacing oxidized bases (base excision repair or BER) or for nucleotides that contain oxidized bases (nucleotide excision repair or NER) in DNA. In RNA, the major process to deal with 8-oxoguanosine is to destroy the damaged RNA. There are actually several overlapping and redundant repair pathways for 8-oxoguanosine, suggesting that this mutation is particularly damaging and must be dealt with for proper cell function.
It is when the body’s sensing and repair mechanisms don’t work that the problems begin. Therefore, science needs to find better ways to tell when the natural processes aren’t working and develop artificial ways to reverse the damage. A 2013 review is showing the way to detecting mutated guanines in bodily fluids and tissues.
Specifically, this study looked at methods of detecting 8-oxoguanosine levels in plasma, urine, and cerebrospinal fluid and what those changes might mean. The levels found represent a balance between the production and repair of the mutations, so an increase means that more mistakes are being made, or fewer are being repaired. Either way, it means that something must be done.
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This is a cartoon showing RNA processing. IT IS NOT TO BE
CONFUSED WITH RNA EDITING!! In processing of eukaryotic
mRNAs, the front end (5’ terminus) is capped so it will last
longer. Then the end is augmented with a bunch of A’s, called
the poly-A tail. Finally, the introns are removed and the
exons (the parts that code for a protein) end up in a
continuous sequence.
But what about nonstandard bases that are actually supposed to be in nucleic acids? The vast majority of these are found in the RNAs and help to point out yet another exception. You think that the RNA transcribed from DNA is the same RNA that functions or is translated to protein? Not always.
RNA editing takes place all the time, where RNA bases are changed after the RNA is transcribed from DNA. In the majority of cases, the RNA editing modifies a standard nucleoside to another standard nucleoside, or add/subtract nucleotides.
Insertion/deletion edits for uracils can increase or decrease the length of the transcript. The mRNA is paired with a guide RNA(gRNA) and base-pairing takes place. For insertion, when there is a mismatch between the mRNA and the gRNA, the editosome inserts a U, so the mRNA transcript gets longer. In deletion editing, if there is an unpaired U in the mRNA, it gets cut out, so the transcript gets shorter.
This was first discovered in a parasite called Trypanosoma brucei, the causative agent of African Sleeping Sickness. There are so many positions at which these insertions/deletions take place that it has come to be known as pan-editing.
In other cases, the editing takes the form of C being replaced by a U. In some cases this results in a protein sequence different than that coded for by the DNA - on purpose!! If that isn’t an exception, I don’t know what is. Other times, the changing of a C to a U creates a stop codon.
In the human apolipoprotein B transcript, the intestinal version undergoes the C to U editing and creates a stop codon, so the apolipoprotein B is 48 kD in mass (B48). In the liver, no editing takes place, so the protein is much larger (B100).
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Here are two examples of RNA editing. The top image
shows the insertion/deletion mechanism, where a guide
RNA binds to the mRNA and where there are mismatches
a U is inserted and where there are unmatched U’s, they
are removed. The bottom example is an example where
a base is changed, and this changes the codon, so a
different amino acid is inserted when translated.
There is a lot of C to U editing in plants – I mean, a lot. So much editing goes on that there is now a 2013 database and algorithm to do nothing but predict C to U and U to C edits. Yes, there are U to C edits as well, but only in plant mitochondria and plastids. As far as is known, U to C edits work to destroy stop codons.
Then there is A to I editing. Wait you say, there’s no I in nucleic acids (well, there are actually two “i”s, but you know what I mean). “I” stands for inosine, the first specialized Lincoln Log and our first nonstandard nucleoside. Adenosine (A) is deaminated to form an inosine (I).
There are many functions for inosine editing. Changes from A to I in mRNA alter the protein made since the inosines get read as G’s. Genomically coded A’s end up being read as G’s in the mRNA, and this it changes the gene product! We have many more inosine changes than other primates do. Many of these A to I edits in humans are related to brain development and are a big reason why we are smarter than chimps.
There is also A to I editing in regulatory RNAs called miRNAs (micro RNA). The miRNAs suppress (prevent) translation of some transcripts, but editing of the pre-miRNA makes it bind less well to protein complexes that process the pre- to mature miRNA. More editing mean less binding of miRNAs, which leads to decreased regulation, more transcript translation, and increased protein. This may be one way A to I editing increases human brain power.
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Micro RNA is important for controlling the amount of a
transcript that will be translated to protein. The miRNA
can be edited, which will change the amount that is
processed by the protein complex, and therefore changes
the amount that is incorporated into the complex
that will degrade mRNAs.
The search is on to discover the regulation of which A’s get turned to I’s in several types of RNAs ; called the inosome (like genome). The inosome is yet another code we haven’t figured out yet. But inosine doesn’t have to bein a nucleic acid to have an effect. Sometimes it functions just by itself.
Inosine and adenosine accumulate extracellularly during hypoxia/ischaemia (lack of oxygen or blood flow) in the brain and may act as neuroprotectants. A new study extends this protective action to the spinal cord in rats in a hypoxic environment. To characterize hypoxia-evoked A and I accumulation, they examined the effect of hypoxia on the extracellular levels of adenosine and inosine in isolated spinal cords from rats. "Isolated" means the rats and their spinal cords were not necessarily in the same room at the time - so it could be a while before this helps humans.
But perhaps the most common use for I is to alter tRNA binding to amino acids and to the target codons. A to I editing can occur in the anticodon, and change which amino acid is placed in the growing peptide. This is especially true in many organisms for the amino acid isoleucine. Many tRNAs will insert an isoleucine into the protein only when the anticodon of the tRNA has been edited to contain an I in the first position (equivalent to the wobble position of the mRNA codon).
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This menacing creature is a worm that lives at the bottom
of the Ocean in the Sea of Cortez. It thrives in the methane
ice on the ocean floor, making it a psychrophile. It can’t
even survive or reproduce if keep above freezing.
What is more, there are other nonstandard nucleosides that serve similar functions, usually with isoleucine or methionine amino acids. Agamantidine is present in many archaeal anticodons and codes for isoleucine. Agamantidine is also present at other points in the tRNA for isoleucine and is important for adding the isoleucine amino acid to the tRNA.
Other nonstandard (modified) nucleosides also work in tRNAs. Lysidine, dihydrouridine, and pseudouridine are some of the more common specialized Lincoln Logs – or maybe we should stick to calling them nonstandard nucleosides. They can be found in the tRNAs of organisms from each of the three domains of life (archaea, bacteria, and eukaryotes). For example, psycrophiles– organisms that grow at very low temperatures – have 70% more dihydrouridines because they help the tRNAs to flex as they need to, even at subfreezing temperatures.
Found mostly in tRNAs, but not exclusively in tRNAs, there are over 100 non-standard nucleosides. Many times they function to increase tRNA binding to transcripts via the anticodon-codon, or increase the binding of the amino acid to the tRNA. They ultimately work to increase translation efficiency. They are weird and are exceptions, but we can’t live without them.
Next week we can spend some time talking about exceptions in the realm of lipids, the last of our four biomolecules.
Paz-Yaacov N, Levanon EY, Nevo E, Kinar Y, Harmelin A, Jacob-Hirsch J, Amariglio N, Eisenberg E, & Rechavi G (2010). Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proceedings of the National Academy of Sciences of the United States of America, 107 (27), 12174-9 PMID: 20566853
Takahashi T, Otsuguro K, Ohta T, & Ito S (2010). Adenosine and inosine release during hypoxia in the isolated spinal cord of neonatal rats. British journal of pharmacology, 161 (8), 1806-16 PMID: 20735412
Lenz H, & Knoop V (2013). PREPACT 2.0: Predicting C-to-U and U-to-C RNA Editing in Organelle Genome Sequences with Multiple References and Curated RNA Editing Annotation. Bioinformatics and biology insights, 7, 1-19 PMID: 23362369
Poulsen HE, Nadal LL, Broedbaek K, Nielsen PE, & Weimann A (2013). Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochimica et biophysica acta PMID: 23791936
Wang P, Fisher D, Rao A, & Giese RW (2012). Nontargeted nucleotide analysis based on benzoylhistamine labeling-MALDI-TOF/TOF-MS: discovery of putative 6-oxo-thymine in DNA. Analytical chemistry, 84 (8), 3811-9 PMID: 22409256
For more information or classroom activities, see:
RNA editing –
http://hstalks.com/main/view_talk.php?t=631&r=22&j=755&c=252
http://dna.kdna.ucla.edu/RNA/index.aspx
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/RNA_Editing.html
http://phys.org/news/2013-09-largest-accurate-rna-sites.html
http://www.ncbi.nlm.nih.gov/pubmed/8833435
http://www.nobelprize.org/educational/medicine/dna/a/splicing/rna_editing.html
http://freethoughtblogs.com/pharyngula/2013/08/26/magic-rna-editing/
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=15&ved=0CEUQFjAEOAo&url=http%3A%2F%2Fwww.sequenceontology.org%2Fabout%2Fso_workshop_plasmid%2Frna_editing.pdf&ei=aO9eUqzPIMeSyAGshoG4Cg&usg=AFQjCNHMKry2jkUOwkIbuYQE3mx6WDv1XQ&sig2=satVhcjlPzBxPOqzpRO56g&bvm=bv.54176721,d.aWc
https://www.mdc-berlin.de/1158081/en/research/research_teams/rna_editing_and_hyperexcitability_disorders
Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites has been published on http://www.michalbrzezinski.org/blog/largest-most-accurate-list-of-rna-editing-sites/
Largest, most accurate list of RNA editing sites
Largest, most accurate list of RNA editing sites
Researchers have compiled the largest and most rigorously validated list to date of the genetic sites in fruit flies where RNA transcribed from DNA is then edited by an enzyme to affect a wide variety of fundamental biological functions. The list yielded several biological insights and can aid further research on RNA transcription because flies are a common model in that work.
http://feedproxy.google.com/~r/sciencedaily/~3/uUahvFBdzIw/130929142735.htm
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