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Tuesday, June 12, 2007

RNA revision

Welcome to meepers anonymous’s RNA revision tutorial. You better read this article if you want to pass the exam!

Ribozymes and their function:

Ok, first we must all understand DNA→ mRNA→Protein. I originally explained this by saying DNA is a library & genes are recipe books in the library which tell cells how to make proteins. When a cell wants to make a protein, it used a protein called RNA polymerase to make a photocopy of the gene. This photocopy is called mRNA. Unlike DNA, mRNA is single stranded not double. The cell reads the photocopy & makes the protein accordingly. The more photocopies(mRNA), the more protein is made.

But how did life arise? You need mRNA to make protein but you need a protein to make mRNA. In other words, you need instructions to make a photocopying machine but need a photocopying machine to print the instructions. That’s where ribozymes come in.


Other function of RNA :

Not all RNA lies around the cell waiting to be made into protein. Some, like ribozymes have other talents,. Ribozymes are RNA which can also act like proteins. They can catalyse cleavage of mRNA. They don’t just cleave any mRNA, they only cleave those with a complementary sequence. Remember that mostly RNA is single stranded, like one side of a zipper, if it finds another mRNA which is complementary (the other half of the zipper) they bind & the ribozyme cleaves the mRNA. There are 3 types of ribozymes, the one in Bree’s dad book was a hairpin ribozyme. Hairpin ribozymes are not found in humans.

Other RNA can cleave mRNA but not on their own, such as siRNA (short interfering RNA). siRNA are short pieces of RNA which bind to a protein complex called RISC. When together, the siRNA binds to mRNA which is complementary, RISC then cleaves the bound mRNA. Think of siRNA as a stencil and the RISC complex as the scalpel. The siRNA determines which pattern (mRNA) is cut and the RISC does the cutting. Other RNA like shRNA (short hairpin RNA) can do the same as siRNA. shRNA is found in humans.

Now this is where jargon causes confusion. Some say hairpin ribozymes and shRNA are the same thing. I think they are different. One can cleave on its own and is not in humans, the other needs proteins and is found in humans. Did the Creators make a mistake? Or are they just trying to confuse us with scientific jargon?


Ribozymes=fountain of youth:

So why should we give a stuff about ribozymes? Well remember that when expressing a gene & making protein, more mRNA = more protein. Therefore if you want to stop gene expression & protein production, you would target the mRNA. Ribozymes can cut up specific mRNA and stop expression of genes. What kind of mRNA would we target?

  1. Viruses: Viruses are composed of DNA or RNA. To survive, they invade a cell, make more virus particles then infect more cells. If you made ribozymes specific for a virus DNA/RNA, then you could destroy it before it could replicate.
  2. Cancer genes: Because cancer cells are able to grow uncontrollably most cancer mutations are in genes which control cell division. These mutations can cause overproduction proteins which tell the cell to divide. One could design ribozymes which target the RNA of these overproduced proteins and possibly hinder cancer progression.
  3. Age dependent genes: Some genes are repressed after we reach a certain age contributing to the aging process. It is possible to use ribozymes to target these repressors & allow the repressed genes to be expressed again. E.g. At the end of chromosomes are regions called telomeres. Every time a cell divides, a bit of the telomere is lost. As we get older, the telomeres eventually run out, stopping cell division. Telomerase is an enzyme which can make telomeres longer. It is repressed in adults. However we could possibly use ribozymes to stop its repression.

Remember in the HoO questionnaire “Do you think aging is a treatable disease?” all the above demonstrate how ribozymes can help act against age related genetic components! (the last one is a little far fetched). We can produce ribozymes synthetically so the idea of harvesting them from Bree seems unnecessary. However, Bree is producing high levels of a particular ribozyme with no immediate side effects. So perhaps the HoO is interested in how a human can overexpress ribozymes harmlessly.


A cure for Bree?

It has been suggested that Bree’s dad was trying to give her something to lower her ribozyme levels. But what was it? We thought it might be siRNA specific for her overexpressed ribozyme. siRNA sequences can easily be designed & sent to biotech companies to be produced. If this is so, Bree’s dad would have hopefully left the siRNA sequence in his notebook which means B&D could order more from the company.

Alternatively, often genes are not expressed unless the cell is sent a certain signal. It could be that Bree’s body is sending too many signals for ribozyme production. Perhaps Bree’s dad found out a way to counteract this.

Both of these methods are 1. Not permanent & 2. Assume trait negative = lower ribozyme levels. But what if trait negative means not having the mutation at all? How can we remove a mutation found in every cell in the entire body? Well, not really. However, if we “suspend our disbelief” & assume the ribozyme is only produced in the red blood cell (RBC) we could try replacing all her RBCs. Such procedures are seen for patients with blood cancer. RBC’s are constantly produced from stem cells in the bone marrow. Patients undergo chemotherapy to kill these stem cells & then fresh stem cells are transplanted in as a replacement. However this is a risky procedure & not something B &D can pull off, even if Sarah does hold the camera.

For more articles see RNA TODAY www.RNAtoday.blogspot.com

10 comments:

  1. very cool....i think we are making progress:)

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  2. I have only skimmed so far, but wow, great job. It might be helpful to link to the several previous articles, either here or on the new blog page.

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  3. Sirna Therapeutics has been at the forefront of efforts to create RNAi-based therapeutics, medicines which could significantly alter the treatment of disease. RNAi-based therapeutics selectively catalyze the destruction of the RNA transcribed from an individual gene. This enables an entirely novel approach to discovering drugs with the potential to produce highly specific, potent, and long-lasting effects.

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  4. All the previous articles are already on rna today. Also there are some good wiki links for anyone who wants to research the topic.

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  5. Yea, i think we are now ready for anything they throw at us.

    Bring it writers!!!!! We need something hard to really get out teeth into:)

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  6. These are some great animations explaining transcription and translation.

    http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a1.html
    http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a2.html
    http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a3.html

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  7. Thanks liz. We added those to a newer post along with a video. We really appreciate the time you took to provide those great links!!!!!

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  8. No problem, model. The TA for my biomolecular engineering class gave them to us this past semester, and I found them really useful. Glad they're helpful for this too. (That class has weird connections to lg15...when the professor started talking about Epogen I literally gasped. XD)

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