BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: RNA

i-motif: A new form of DNA discovered

Australian researchers have discovered a new structure of DNA called i-motif. This form of DNA is in the shape of a twisted knot, vastly different from the conventional double helix model. i-motif basically looks like a four-stranded knot of DNA. In the i-motif form, the C bases on the same strand of DNA bind to each other instead of their complementary pairs.

File:G-quadruplex.gif

(Photo: Wikimedia Commons)

How did scientists discover i-motif?

i-motif previously haven’t been seen before, apart from in in-vitro (which means under laboratory conditions and not in the natural world) To detect i-motif, scientists used a tool made up of a fragment of an antibody molecule. This antibody could recognize and attach to i-motifs. Researchers showed that the i-motif structures mostly formed at the G1 phase -when mRNA is synthesized- in a cells life cycle. The i-motifs show up in promoter regions and in telomeres in the chromosome.

While scientists aren’t really sure the actual reason for their existence, some researchers suggest that they are there to help switch genes on and off and affect whether or not a gene is actively read.

Whatever the reason for their existence, they have potential to play an important role in how and when DNA is read. Prof Marcel Dinger at the Garvan Institute for Medical Research says, “It’s exciting to uncover a whole new form of DNA in cells — and these findings will set the stage for a whole new push to understand what this new DNA shape is really for, and whether it will impact on health and disease.”

Closer to Reality: Gene Editing Technology

In August of 2017, scientists in the United States were successful in genetically modifying human embryos, becoming the first to use CRISPR-cas9 to fix a disease causing DNA replication error in early stage human embryos. This latest test was the largest scale to take place and proved that scientists were able to correct a mutation that caused a genetic heart condition called hypertrophic cardiomyopathy.

CRISPR-cas9 is a genome editing tool that is faster and more economical than othe r DNA editing techniques. CRISPR-cas9 consists of two molecules, an enzyme called cas9 cuts strands of DNA so pieces of DNA can be inserted in specific areas. RNA called gRNA or guide RNA guide the cas9 enzyme to the locations where impacted regions will be edited.

(Source: Wikipedia Commons)

 

Further tests following the first large-scale embryo trial will attempt to solidify CRISPR’s track record and bring it closer to clinical trials. During the clinical trials, scientists would use humans- implanting the modified embryos in volunteers and tracking births and progress of the children.

Gene editing has not emerged without controversy. While many argue that this technology can be used to engineer the human race to create genetically enhanced future generations, it cannot be overlooked that CRISPR technology is fundamentally for helping to repair genetic defects before birth. While genetic discrimination and homogeneity are possible risks, the rewards from the eradication of many genetic disorders are too important to dismiss gene editing technology from existing.

 

What does the future hold for CRISPR-Cas9?

Genome editing, or the technologies in which scientists can change the DNA of an organism, is on the rise, especially with its latest development, CRISPR-Cas9, the most efficient method of all of the methods to edit DNA.

Like many other discoveries in science, CRISPR-Cas9 was discovered through nature. Scientists learned that certain bacteria capture snippets of DNA from invading viruses, making DNA segments called CRISPR arrays, helping them remember the virus to prepare for future invasions of that virus. When they are confronted with that virus again, RNA segments from the CRISPR arrays are created which target the DNA of the virus, causing the enzyme Cas9 to cut the virus’ DNA apart, which would destroy the virus.

 

We use the same method in genome editing with CRISPR-Cas9 by creating RNA that binds to a specific sequence in a DNA strand and the Cas9, causing the Cas9 to cut the DNA at that specific sequence. Once this is done, the scientists create a sequence to replace the one that was cut to get the desired genome.

This technology is most prominently used to attempt to treat diseases, where the somatic cells’ genomes are altered which affect tissues, as well as prevent genetic diseases where the sperm or egg’s genome is changed. However, the latter causes some serious ethical concerns of whether we should use this technology to enhance human traits. But this begs the question that if we start using it more and more to prevent genetic diseases, will this open the door for it to be used in new ways?

CRISPRainbow

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)and CRISPR-associated protein 9 complex has become one of the biggest technological advances in science. This genome editing technology has taken multiple advances toward closer research into studies of embryonic development to cancer. CRISPRainbow, a modification to CRISPR where the Cas9 is mutated, allows researchers to label up to seven different genomic locations in live cells.
CRISPR has been used for editing genomes, however, research specialist Hanhui Ma and his team has used it to label DNA and track the movement of DNA in live cells. With this new research, we can find the precise genomic location in order to understand the movement of chromosomes. This is important because the genes that create our biological make-up and control our health do so by their location in the 3-D space.
Currently, with CRISPR, we can only label three genomic locations at a time in each cell. It has extremely challenged scientists to label more sites because it would require cells to be mixed in formaldehyde, which would kill them, making it impossible to observe the chromosome’s structure when stimulated by a response.
The new Cas9 mutation causes the nuclease to deactivate, so it only binds to DNA and doesn’t cut the genome. Then, the CRISPRainbow is docked into location by the guide RNA which can be programmed technologically. Research specialist, Hanhui Ma was able to figure out a way to implement computational coloring. Each guide RNA would include one of the three primary fluorescent proteins: red, green or blue which then can be observed in real time under a microscope. Pretty cool, right? Well, guess what? It doesn’t stop here. Ma decided to go even further in his research and attach a second fluorescent protein to the guide RNA. Ma could then combine the three primary colors to generate three additional labels: cyan, magenta, and yellow. From the primary colors, he was able to achieve white as the seventh color.
CRISPRainbow can track the challenging and dynamic movement of genomes that may lead to biological consequences. Research Scientist, Hanhui Ma, states “With this technology, we can visualize different chromosome loci at different points in time.” We can observe the structural changes in chromosomes overtime with help us understand their relation to health and disease. So why do you think they called is CRISPRainbow? What kind of diseases can we track with this new technology? What more can CRISPRainbow do in the near future?

Questioning one of the most widely-held beliefs about the origins of life!

Two scientists, Dr. Charles Carter, of University of North Carolina at Chapel Hill, and Peter Wills, a physics professor at the University of Auckland, are challenging one of the most widely-held beliefs in the world of science.

A widely accepted hypothesis of the origin of life is called the “RNA-world” hypothesis, which states that life began from nucleic acids and only evolved later into proteins. However, in two recent studies, scientists Carter and Wills have found that this hypothesis is false, and have named their findings the “peptide-RNA” hypothesis. They believe their findings are much more probable and realistic. They argue that RNA could not be the source of biological life on earth because it lacks an important characteristic, called “reflexivity”. This means RNA lacks the ability to form the feedback loop that is necessary to lead to eventual life forms.

Source: https://pixabay.com/en/dna-string-biology-3d-1811955/

At the core of their “peptide-RNA” hypothesis is that the remnants of ancient enzymes are still found in all living organisms today. These ancient enzymes are called aminoacyl-tRNA-synthetases (aaRSs). These 20 aaRSs enzymes are broken into 2 structurally distinct families which each are exact opposites of each other. Being that these enzymes are so simple in structure, Cater and Wills believe they are the basis of biological life.

So, which theory do you believe, the “RNA-world” hypothesis or the “peptide-RNA” hypothesis?

Original Article: https://www.sciencedaily.com/releases/2017/11/171101160756.htm

A Second Theory: Is the RNA World Hypothesis Wrong?

Introduction

Prior to recent research, scientists strongly supported the “RNA world” hypothesis, a theory that claims that DNA derived from RNA, and that RNA therefore provided the basis for life as we know it. The evidence of this new study under scientists at The Scripps Research Institute leads to an alternate theory that challenges this previous mode of thinking. This study is intriguing not only because it challenges what has mostly been accepted as factual truth by most scientists, but also because it attempts to solve the question of where and how first life developed.

Background: The “RNA world” hypothesis

The “RNA world” hypothesis dates back to over 30 years ago. Proposed independently by Carl Woese, Francis Crick, and Leslie Orgel, it essentially is a theory that states that RNA existed before modern cells, and stored genetic information and catalyzed chemical reactions within earlier cells. This theory further claims that DNA came later and only then contained the genetic material. It also infers that proteins served as a catalyst much later, only fulfilling this role once RNA evolved. The evidence that supports this theory lies with the chemical differences that distinguish RNA from DNA. RNA can be formed from formaldehyde (HCHO) which is chemically simple, especially in comparison to the much more complicated sugar deoxyribose. In a reaction catalyzed by a specific enzyme, deoxyribose is produced from ribose which also indicates the possibility that DNA comes directly after the structurally more simple and single helix RNA.

Recent Studies

Researchers believe that if this theory is correct, RNA nucleotides and DNA backbones would have mixed to create “heterogeneous” (or a product resulting from differing “parents” with unique charateristics) strands. The resulting “chimeras” (an organism composed of cells from different zygotes leading to subtle variations in form) would be an intermediate step in the transition to RNA if stable, however the study shows a decrease in stability (specifically in thermal stability or the ability to function at high temperatures) when the backbone is shared between the two nucleic acids. The researchers attribute this instability to a slight difference between the sugar in RNA and the sugar in DNA. As a result, if the RNA theory had been true, the chimeras would have died off. This proves that evolution has lead to a system where enzymes have developed to maintain the system of “homogenous” molecules, keeping RNA and DNA separate since they function much better separate from one another. Since these enzymes are fairly “new” in terms of the span of the existence of DNA and RNA, it is highly unlikely that RNA was able to transition to newly developed DNA. Without any mechanisms to keep DNA and RNA separate, it is logical to conclude that RNA does not predicate DNA. This concept is reminiscent of the endosymbiont theory that discusses the possible reason for the unique qualities of mitochondria and chloroplasts in that both theories rely on existing knowledge about these unique structures and how each component might contribute to a different function. Similar to the endosymbiont theory, there is no exact answer as to whether this theory is correct, however through challenging the theory and conducting experiments, we can further develop our understanding of certain biological phenomena.

Conclusion

This alternate theory, on the other hand, proposes a different view that RNA and DNA have coexisted and that one therefore did not develop from the other. While this theory is not completely new, these recent findings regarding instability for a backbone shared between the two nucleic acids provide more evidence for this secondary theory (to the RNA world theory). If this theory is accurate, DNA could have developed its homogenous system much earlier than scientists have predicted up until this point. According to this second theory, after RNA first interacted with DNA it still could have evolved to create DNA. Although scientists will never be able to discover life’s exact origin, these findings can provide insights for biology overall.

images

https://biologydirect.biomedcentral.com/articles/10.1186/1745-6150-7-23

http://www.sciencemag.org/news/2016/05/rna-world-inches-closer-explaining-origins-life

https://www.sciencedaily.com/releases/2016/09/160928153357.htm

http://www.medicinenet.com/script/main/art.asp?articlekey=8905

XRN1: The Virus Hitman

When I think of the words killer and assassin, my mind drifts to shady men in all black equipped with sniper rifles. However, recent research conducted by the University of Idaho and the University of Colorado Boulder has indicated that I should expand that mental list to include XRN1, a gene in saccharomyces cerevisiae which, according to a recent study, kills viruses within the yeast. Upon stumbling onto this subject, I was intrigued because it was a fairly simple procedure that led to a huge discovery. To grasp the significance of such a discovery, one must understand it on a molecular level. XRN1’s duty in yeasts is to create a protein which breaks down old RNA. The image below shows the generic process of the creation of a new protein through gene regulation.

Wikipedia- Regulation of Gene Expression

Wikipedia- Regulation of Gene Expression

Yeasts also contain viral RNA since practically all yeasts are infected by viruses. When scientists removed XRN1 from the yeasts, the viruses within yeasts replicated much faster, and when they expressed high amounts of XRN1, the virus was completely eradicated. This is because the XRN1 gene was inadvertently breaking down the viral RNA, mistakenly taking it for the yeast’s RNA. Scientists continued the research by using XRN1 from other saccharomyces yeast species. The virus continued replicating rapidly but the XRN1 did continue its job of breaking down the yeast’s RNA. This shows that the XRN1 from each yeast species evolves to attack the specific viruses that occur in its host while still maintaining their basic role as the RNA eaters. Scientists are hopeful about this study’s human health implications. Viruses such as Polio and Hepatitis C work by degrading XRN1 and not allowing it to break down RNA, respectively. Dengue Fever also occurs when XRN1 is unable to perform its function of RNA breakdown. These studies on Dengue Fever and Hepatitis C elaborate on the implications of XRN1 not breaking down RNA. Scientists hope that this discovery could lead to the triumph of XRN1 over these viruses. Could this really be the discovery that leads to the first ever Hepatitis C vaccine? Do you think that XRN1’s success against virus in yeasts guarantees eventual success against viruses in humans?

 

Original Article: http://phys.org/news/2016-10-yeast-gene-rapidly-evolves-viruses.html

 

CRISPR-Cas9 Can Now Be Applied to Not Only DNA But RNA

Anyone who has seen the movie Gattaca knows that the plot is set in a futuristic society that is able to edit the human genome. Of course, there’s a reason that it’s set in the future. Scientists of today couldn’t possibly dream of being able to edit genes in our DNA…right?

Well, wrong. Say hello to CRISPR-Cas9. CRISPER-Cas9 is, in short, a highly effective and popular DNA-editing technique that scientists started to use to sequence and edit human genes.

However, thanks to scientists at University of California-San Diego, CRISPR-Cas9 is not only limited to editing DNA. By altering only a few key features, this mechanism can now also be used with RNA, another highly important and fundamental molecule in the human body. CRISPR-Cas9 as of now can be used to track RNA in its movement, such as its many essential roles in protein synthesis. Below is a picture that briefly shows the importance of mRNA and tRNA:

 

Screen Shot 2016-04-11 at 12.01.31 AM

(Source: http://www.proteinsynthesis.org/protein-synthesis-steps/)

It’s an exciting development in that certain diseases, such as cancer and autism, are linked to mutations in RNA. By using CRISPR-Cas9 to their advantage, scientists could study the movement of RNA in the cell—and how and when it gets there—to track any defective RNA that can potentially lead to such diseases and then hopefully develop treatments. Gene Yeo, PhD, an associate professor of cellular and molecular medicine at UC-San Diego, expresses hope that “future developments could enable researchers to measure other RNA features or advance therapeutic approaches to correct disease-causing RNA behaviors”.

Intrigued? Confused? Please leave any comments or questions below!

 

Original Article

Forget DNA, Let’s Talk RNA!

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Photo of RNA (licensing information here)

The genetic code within DNA is responsible for determining who we are and what we are capable of. Because of this, scientists have been interested in cracking the genetic code and finding ways to alter it. There are many diseases linked to DNA, as well as RNA. However, scientists have not been as successful in targeting RNA in living cells as they have been in targeting DNA. Recently, using CRISPR-Cas9, researchers at University of California, San Diego School of Medicine have figured out how to do what has been troubling scientists.

Senior author Dr. Gene Yeo described how the researchers at UCSD have been tracking the movement of RNA throughout cells and plan to measure other RNA features and help to correct disease-causing RNA behaviors using CRISPR-Cas9. The location of RNA in a cell determines whether proteins are produced at the right time and in the right place. When defective RNA transport occurs, diseases ranging from autism to cancer can occur. In order to successfully treat these conditions, researchers must find a way to track and measure the movement of RNA. This process was first seen with DNA: scientists found they could use CRISPR-Cas9 to track and edit genes in mammalian systems. Now, however, Yeo and his colleagues at UC Berkeley have started to target RNA in live cells (RNA-targeted Cas9 or RCas9), as well as DNA in live cells.

When CRISPR-Cas9 is used for normal DNA-involved purposes, researchers design “guide” RNA to match the DNA sequence of the gene Cas9 is targeting. The “guide” RNA then directs the Cas9 enzyme to the target spot in the genome. The Cas9 enzyme then cuts the DNA, which causes the DNA to break in a manner that inactivates the gene. Researchers can also replace the section of the genome next to the cut DNA with a corrected version of the gene. In order to allow Cas9 to work for RNA as well as DNA, work originated by co-author Dr. Jennifer Doudna at UC Berkeley laid a base foundation for researchers to design the PAMmer: a short nucleic acid. The PAMmer works with the “guide” RNA to direct Cas9 to an RNA molecule, instead of DNA.

All in all, CRISPR-Cas9 is responsible for a revolution in genomics with it’s ability to target and modify human DNA. Although this breakthrough is crucial, scientists are now trying to use their lead to target and modify RNA. With an extension on already existing research, there is no doubt that scientists will soon be able to do more than just track RNA. So, let’s forget about DNA and shine a light on RNA for a little while!

Source

Viruses are Like Felons, They Both Get Mugshots

Scientists at the Stanford University School of Medicine and three other schools have just discovered that a bacteria named Marinomonas mediterranea takes “RNA mug shots” to help recognize and defeat harmful viruses. The bacteria can take “RNA mugshots” or “DNA mugshots” depending on whether the invader is RNA-based or DNA-based.

Researchers want to use this technic to genetically form crops that have this virus-identifying property. Another use is to prevent viruses from infecting dairy products.

CRISPR is a new way of editing genomes that relates to this discovery. Bacteria takes pieces of DNA from cells and store them, also like “mugshots”.

RNA help DNA is coding, decoding, and expressing genes. By just getting a snapshot of a virus’ RNA or DNA, bacteria can identify this virus and destroy it in the future.

This finding is very new and so scientists are still studying how it exactly works and what its applications are. How do our readers think about it? Is this a surprising discovering or does it seem obvious? Were you aware that viruses have their own DNA and RNA? How do you think bacteria can apply this technic to other problems in the body, such as the regulation of cell production? Comment below on your scientific observations of this finding!

 

https://pixabay.com/en/virus-microbiology-cell-infection-163471/

Other sources:

https://www.sciencedaily.com/releases/2016/02/160225153423.htm 

http://kalen2utech.com/bacteria-take-rna-mug-shots-of-threatening-viruses/ 

http://www.technewscoverage.com/news/bacteria-take-rna-mug-shots-of-threatening-viruses.html 

 

Protein Structure May Lead to Cure for Ebola

For those who haven’t been keeping up with the latest in viral outbreaks, Ebola has been spreading throughout West Africa and has already taken the lives of 2,600 people since the outbreak in March 2014.  According to the World Health Organization , there are currently no certified vaccines or treatments for Ebola but a new breakthrough may have answers to developing a cure or vaccine for the deadly disease

Scientists at the University of Virginia have gotten their hands on a crystalized structure of the Ebola Nucleoprotein C-Terminal domain, which is an important protein used in replicating the virus.  The tertiary fold of the C-terminal is “unique in the RNA virus world,” claims structural biologist Dr. Zygmunt Derewenda, and this unique fold could ultimately lead to the foundation of drugs to prevent further infections.

The team was able to produce the protein by using E Coli as the protein factory.  So far, the protein demonstrates traits that are extremely unique and unlike other known proteins.  Evidence thus far has shown that the viral nucleoapsid is self assembled by the domain.  Insights and new research that the UVA team is conducting is paving the way to an Ebola anti-viral drug.

 

Ebola Virus Particles

 

Breakthrough in Epigenetics!

 

This file (Arabidopsis thaliana flower) is in public domain, not copyrighted, no rights reserved, free for any use

 

For several dozen years scientists have searched for a way to understand the role of a single RNA strand in gene expression.  Scientists have been without a method to pinpoint 1 type of RNA strand and isolate its effect thus discovering its influence and its corresponding proteins role in influencing the way our bodies work.

However a breakthrough was made this march regarding such obstacles.  A team of scientists from Michigan Technological University discovered a way to turn off small RNA strands in order to figure out what they are up to.  They did this by inserting their own custom DNA strand that codes for something called a small tandem target mimic or “STTM” into a plant known as “Arabidopsis“.  Inside the plant, these DNA strands gave rise to STTM’s that blocked the ability of a target RNA to express itself.  The particular target for the STTM was a type of RNA strand suspected to be involved with facilitating vertical growth of the plant.  The STTM’s stopped the RNA from being able to cut itself into smaller bits, and prompted the target RNA’s to destroy all of its own smaller RNA’s that would normally slice the target RNA.  This effectively lead to the disappearance of the target RNA’s protein products thus resulting in no expression of the gene the target RNA from transcribed from.

The result was outstanding.  “The control Arabidopsis plants grew upward on a central stem with regularly shaped leaves and stems. The mutant plants were smaller, tangled, and amorphous.”

The above process is said to be “a highly effective and versatile tool” for studying the functions of small RNA.  One researcher on the team who discovered this method stated that she intends to use this discovery to study type 2 diabetes.

 

Reference

http://www.sciencedaily.com/releases/2012/03/120301143756.htm

Tricky Viruses

Photo Credit: Foto_di_Signorina Flickr

           Strong viruses, such as HIV, make the body work for them. Researchers in Copenhagen have been studying how these viruses manage to take over the body. The virus takes over one cell and then uses the RNA to influence the DNA, giving the virus complete control over the cell. The RNA of the virus is similar to the RNA of the cell. Therefore, the ribosomes of the cell copy the sequence from the virus instead of the actual RNA. This causes the cell to produce the virus’ proteins.

                The RNA of the virus has what is called a pseudoknot. Pseudoknots are places on the RNA that the ribosomes must decipher before it can move on. The pseudoknot holds the sequence for key destructive proteins of the virus and once the ribosome deciphers it, those proteins are produced. This is how HIV can spread so rapidly in the body and can take such a hold over the host; it doesn’t do any of the work.

Can We Begin with a Moment of Silence?

In today’s world, there are more and more breaks in cancer research, and Dr. Sven Diederichs and his team are one more to add to the list.  Dr. Sven believes that “In many cancers we find that specific non- coding genes are particularly active. Therefore, we want to understand what the RNA molecules transcribed from these genes bring about in the tumor cells.”  Could this be the big answer? After all this time, could it be that it has been RNA molecules sending messages that create cancer.

Dr. Sven and his team came to this hypothesis and therefore created a method to find out the truth called “loss-of-function.”  In this experiment, scientists can silence a gene of a living cell and try to find changes in the cell’s behavior, metabolism, or physiology. They created this method on the use of zinc finger nucleases.

Once the scientist figured out how to make this method work, they were able to, for the first time, completely silence genes. Why is this important to cancer research? Dr. Sven believes that certain genes play a huge role in the development of cancer and are very active in tumor cells. If we have the chance to “shut down” these genes in RNA before they become active, we can ultimately prevent cancer.

In AP Biology class, we are learning about RNA transferring different kinds of information that stimulate cells to perform certain functions based on need, location and ability.  Are all these stimuli good? Or are they sending messages to create tumor cells?

We all know someone that has cancer, whether it’s your brother’s girlfriend’s uncle’s high school girlfriend, a friend of a friend, your best friend or it’s you. Everyone has a reason they want to get rid of such a terrible disease. So would you invest in this research or do you think its impossible to figure out which exact gene is the cause for all cancers?

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