Tag Archives: RNA

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Helping the Honeybees

Agricultural biotechnology giant Monsanto is joining efforts to help the honeybee. Honeybees the world over have been suffering from a widespread and catastrophic condition often referred to a colony collapse disorder.

From Technology Review:

Beekeepers are desperately battling colony collapse disorder, a complex condition that has been killing bees in large swaths and could ultimately have a massive effect on people, since honeybees pollinate a significant portion of the food that humans consume.

A new weapon in that fight could be RNA molecules that kill a troublesome parasite by disrupting the way its genes are expressed. Monsanto and others are developing the molecules as a means to kill the parasite, a mite that feeds on honeybees.

The killer molecule, if it proves to be efficient and passes regulatory hurdles, would offer welcome respite. Bee colonies have been dying in alarming numbers for several years, and many factors are contributing to this decline. But while beekeepers struggle with malnutrition, pesticides, viruses, and other issues in their bee stocks, one problem that seems to be universal is the Varroa mite, an arachnid that feeds on the blood of developing bee larvae.

“Hives can survive the onslaught of a lot of these insults, but with Varroa, they can’t last,” says Alan Bowman, a University of Aberdeen molecular biologist in Scotland, who is studying gene silencing as a means to control the pest.

The Varroa mite debilitates colonies by hampering the growth of young bees and increasing the lethality of the viruses that it spreads. “Bees can quite happily survive with these viruses, but now, in the presence of Varroa, these viruses become lethal,” says Bowman. Once a hive is infested with Varroa, it will die within two to four years unless a beekeeper takes active steps to control it, he says.

One of the weapons beekeepers can use is a pesticide that kills mites, but “there’s always the concern that mites will become resistant to the very few mitocides that are available,” says Tom Rinderer, who leads research on honeybee genetics at the U.S. Department of Agriculture Research Service in Baton Rouge, Louisiana. And new pesticides to kill mites are not easy to come by, in part because mites and bees are found in neighboring branches of the animal tree. “Pesticides are really difficult for chemical companies to develop because of the relatively close relationship between the Varroa and the bee,” says Bowman.

RNA interference could be a more targeted and effective way to combat the mites. It is a natural process in plants and animals that normally defends against viruses and potentially dangerous bits of DNA that move within genomes. Based upon their nucleotide sequence, interfering RNAs signal the destruction of the specific gene products, thus providing a species-specific self-destruct signal. In recent years, biologists have begun to explore this process as a possible means to turn off unwanted genes in humans (see “Gene-Silencing Technique Targets Scarring”) and to control pests in agricultural plants (see “Crops that Shut Down Pests’ Genes”).  Using the technology to control pests in agricultural animals would be a new application.

In 2011 Monsanto, the maker of herbicides and genetically engineered seeds, bought an Israeli company called Beeologics, which had developed an RNA interference technology that can be fed to bees through sugar water. The idea is that when a nurse bee spits this sugar water into each cell of a honeycomb where a queen bee has laid an egg, the resulting larvae will consume the RNA interference treatment. With the right sequence in the interfering RNA, the treatment will be harmless to the larvae, but when a mite feeds on it, the pest will ingest its own self-destruct signal.

The RNA interference technology would not be carried from generation to generation. “It’s a transient effect; it’s not a genetically modified organism,” says Bowman.

Monsanto says it has identified a few self-destruct triggers to explore by looking at genes that are fundamental to the biology of the mite. “Something in reproduction or egg laying or even just basic housekeeping genes can be a good target provided they have enough difference from the honeybee sequence,” says Greg Heck, a researcher at Monsanto.

Read the entire article here.

Image: Honeybee, Apis mellifera. Courtesy of Wikipedia.

BigBang

From RNA Chemistry to Cell Biology

Each day we inch towards a better scientific understanding of how life is thought to have begun on our planet. Over the last decade researchers have shown how molecules like the nucleotides that make up complex chains of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid) may have formed in the primaeval chemical soup of the early Earth. But it’s altogether a much greater leap to get from RNA (or DNA) to even a simple biological cell. Some recent work sheds more light and suggests that the chemical to biological chasm between long-strands of RNA and a complex cell may not be as wide to cross as once thought.

From ars technica:

Origin of life researchers have made impressive progress in recent years, showing that simple chemicals can combine to make nucleotides, the building blocks of DNA and RNA. Given the right conditions, these nucleotides can combine into ever-longer stretches of RNA. A lot of work has demonstrated that RNAs can perform all sorts of interesting chemistry, specifically binding other molecules and catalyzing reactions.

So the case for life getting its start in an RNA world has gotten very strong in the past decade, but the difference between a collection of interesting RNAs and anything like a primitive cell—surrounded by membranes, filled with both RNA and proteins, and running a simple metabolism—remains a very wide chasm. Or so it seems. A set of papers that came out in the past several days suggest that the chasm might not be as large as we’d tend to think.

Ironing out metabolism

A lot of the basic chemistry that drives the cell is based on electron transport, typically involving proteins that contain an iron atom. These reactions not only create some of the basic chemicals that are necessary for life, they’re also essential to powering the cell. Both photosynthesis and the breakdown of sugars involve the transfer of electrons to and from proteins that contain an iron atom.

DNA and RNA tend to have nothing to do with iron, interacting with magnesium instead. But some researchers at Georgia Tech have considered that fact a historical accident. Since photosynthesis put so much oxygen into the atmosphere, most of the iron has been oxidized into a state where it’s not soluble in water. If you go back to before photosynthesis was around, the oceans were filled with dissolved iron. Previously, the group had shown that, in oxygen-free and iron rich conditions, RNAs would happily work with iron instead and that its presence could speed up their catalytic activity.

Now the group is back with a new paper showing that if you put a bunch of random RNAs into the same conditions, some of them can catalyze electron transfer reactions. By “random,” I mean RNAs that are currently used by cells to do completely unrelated things (specifically, ribosomal and transfer RNAs). The reactions they catalyze are very simple, but remember: these RNAs don’t normally function as a catalyst at all. It wouldn’t surprise me if, after a number of rounds of evolutionary selection, an iron-RNA combination could be found that catalyzes a reaction that’s a lot closer to modern metabolism.

All of which suggests that the basics of a metabolism could have gotten started without proteins around.

Proteins build membranes

Clearly, proteins showed up at some point. They certainly didn’t look much like the proteins we see today, which may have hundreds or thousands of amino acids linked together. In fact, they may not have looked much like proteins at all, if a paper from Jack Szostak’s group is any indication. Szostak’s found that just two amino acids linked together may have catalytic activity. Some of that activity can help them engage in competition over another key element of the first cells: membrane material.

The work starts with a two amino acid long chemical called a peptide. If that peptide happens to be serine linked to histidine (two amino acids in use by life today), it has an interesting chemical activity: very slowly and poorly, it links other amino acids together to form more peptides. This weak activity is especially true if the amino acids are phenylalanine and leucine, two water-hating chemicals. Once they’re linked, they will precipitate out of a water solution.

The authors added a fatty acid membrane, figuring that it would soak up the reaction product. That definitely worked, with the catalytic efficiency of serine-histidine going up as a result. But something else happened as well: membranes that incorporated the reaction product started growing. It turns out that its presence in the membrane made it an efficient scrounger of other membrane material. As they grew, these membranes extended as long filaments that would break up into smaller parts with a gentle agitation and then start growing all over again.

In fact, the authors could set up a bit of a Darwinian competition between membranes based on how much starting catalyst each had. All of which suggests that proteins might have found their way into the cell as very simple chemicals that, at least initially, weren’t in any way connected to genetic and biochemical functions performed by RNA. But any cell-like things that evolved an RNA that made short proteins could have a big advantage over its competition.

Read the entire article here.

BigBang

The Missing Linc

LincRNA that is. Recent discoveries hint at the potentially crucial role of this new class of genetic material in embryonic development, cell and tissue differentiation and even speciation and evolution.

[div class=attrib]From the Economist:[end-div]

THE old saying that where there’s muck, there’s brass has never proved more true than in genetics. Once, and not so long ago, received wisdom was that most of the human genome—perhaps as much as 99% of it—was “junk”. If this junk had a role, it was just to space out the remaining 1%, the genes in which instructions about how to make proteins are encoded, in a useful way in the cell nucleus.

That, it now seems, was about as far from the truth as it is possible to be. The decade or so since the completion of the Human Genome Project has shown that lots of the junk must indeed have a function. The culmination of that demonstration was the publication, in September, of the results of the ENCODE project. This suggested that almost two-thirds of human DNA, rather than just 1% of it, is being copied into molecules of RNA, the chemical that carries protein-making instructions to the sub-cellular factories which turn those proteins out, and that as a consequence, rather than there being just 23,000 genes (namely, the bits of DNA that encode proteins), there may be millions of them.

The task now is to work out what all these extra genes are up to. And a study just published in Genome Biology, by David Kelley and John Rinn of Harvard University, helps do that for one new genetic class, a type known as lincRNAs. In doing so, moreover, Dr Kelley and Dr Rinn show just how complicated the modern science of genetics has become, and hint also at how animal species split from one another.

Lincs in the chain

Molecules of lincRNA are similar to the messenger-RNA molecules which carry protein blueprints. They do not, however, encode proteins. More than 9,000 sorts are known, and most of those whose job has been tracked down are involved in the regulation of other genes, for example by attaching themselves to the DNA switches that control those genes.

LincRNA is rather odd, though. It often contains members of a second class of weird genetic object. These are called transposable elements (or, colloquially, “jumping genes”, because their DNA can hop from one place to another within the genome). Transposable elements come in several varieties, but one group of particular interest are known as endogenous retroviruses. These are the descendants of ancient infections that have managed to hide away in the genome and get themselves passed from generation to generation along with the rest of the genes.

Dr Kelley and Dr Rinn realised that the movement within the genome of transposable elements is a sort of mutation, and wondered if it has evolutionary consequences. Their conclusion is that it does, for when they looked at the relation between such elements and lincRNA genes, they found some intriguing patterns.

In the first place, lincRNAs are much more likely to contain transposable elements than protein-coding genes are. More than 83% do so, in contrast to only 6% of protein-coding genes.

Second, those transposable elements are particularly likely to be endogenous retroviruses, rather than any of the other sorts of element.

Third, the interlopers are usually found in the bit of the gene where the process of copying RNA from the DNA template begins, suggesting they are involved in switching genes on or off.

And fourth, lincRNAs containing one particular type of endogenous retrovirus are especially active in pluripotent stem cells, the embryonic cells that are the precursors of all other cell types. That indicates these lincRNAs have a role in the early development of the embryo.

Previous work suggests lincRNAs are also involved in creating the differences between various sorts of tissue, since many lincRNA genes are active in only one or a few cell types. Given that their principal job is regulating the activities of other genes, this makes sense.

Even more intriguingly, studies of lincRNA genes from species as diverse as people, fruit flies and nematode worms, have found they differ far more from one species to another than do protein-coding genes. They are, in other words, more species specific. And that suggests they may be more important than protein-coding genes in determining the differences between those species.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image: Darwin’s finches or Galapagos finches. Darwin, 1845. Courtesy of Wikipedia.[end-div]

BigBang

Your Molecular Ancestors

[div class=attrib]From Scientific American:[end-div]

Well, perhaps your great-to-the-hundred-millionth-grandmother was.

Understanding the origins of life and the mechanics of the earliest beginnings of life is as important for the quest to unravel the Earth’s biological history as it is for the quest to seek out other life in the universe. We’re pretty confident that single-celled organisms – bacteria and archaea – were the first ‘creatures’ to slither around on this planet, but what happened before that is a matter of intense and often controversial debate.

One possibility for a precursor to these organisms was a world without DNA, but with the bare bone molecular pieces that would eventually result in the evolutionary move to DNA and its associated machinery. This idea was put forward by an influential paper in the journal Nature in 1986 by Walter Gilbert (winner of a Nobel in Chemistry), who fleshed out an idea by Carl Woese – who had earlier identified the Archaea as a distinct branch of life. This ancient biomolecular system was called the RNA-world, since it consists of ribonucleic acid sequences (RNA) but lacks the permanent storage mechanisms of deoxyribonucleic acids (DNA).

A key part of the RNA-world hypothesis is that in addition to carrying reproducible information in their sequences, RNA molecules can also perform the duties of enzymes in catalyzing reactions – sustaining a busy, self-replicating, evolving ecosystem. In this picture RNA evolves away until eventually items like proteins come onto the scene, at which point things can really gear up towards more complex and familiar life. It’s an appealing picture for the stepping-stones to life as we know it.

In modern organisms a very complex molecular structure called the ribosome is the critical machine that reads the information in a piece of messenger-RNA (that has spawned off the original DNA) and then assembles proteins according to this blueprint by snatching amino acids out of a cell’s environment and putting them together. Ribosomes are amazing, they’re also composed of a mix of large numbers of RNA molecules and protein molecules.

But there’s a possible catch to all this, and it relates to the idea of a protein-free RNA-world some 4 billion years ago.

[div class=attrib]Read more after the jump:[end-div]

[div class=attrib]Image: RNA molecule. Courtesy of Wired / Universitat Pampeu Fabra.[end-div]

BigBang

A Simpler Origin for Life

[div class=attrib]From Scientific American:[end-div]

Extraordinary discoveries inspire extraordinary claims. Thus, James Watson reported that immediately after he and Francis Crick uncovered the structure of DNA, Crick “winged into the Eagle (pub) to tell everyone within hearing that we had discovered the secret of life.” Their structure–an elegant double helix–almost merited such enthusiasm. Its proportions permitted information storage in a language in which four chemicals, called bases, played the same role as 26 letters do in the English language.

Further, the information was stored in two long chains, each of which specified the contents of its partner. This arrangement suggested a mechanism for reproduction: The two strands of the DNA double helix parted company, and new DNA building blocks that carry the bases, called nucleotides, lined up along the separated strands and linked up. Two double helices now existed in place of one, each a replica of the original.

[div class=attrib]More from theSource here.[end-div]