Nucleic Acid Origami

RNA is a single-stranded nucleic acid that can fold into more complex and interesting structures than DNA can. This activity will teach you the rules of how RNA folds in living organisms, and how mutations in RNA can change its structure.

Let's try out RNA structure prediction with a set of interesting RNAs from throughout the biological world.

MicroRNA


Open the first RNA, a microRNA, here: microRNA

If you right-click the link above you can also open it in a new tab.

Paste the sequence into the first text box at the RNAfold web-server page.

Next, click Proceed >>

You've just computed the secondary structure for a microRNA hairpin! This hairpin structure is named this because of its resemblance to a "bobby pin".

This shape of the microRNA, as with all RNAs on this page, is an important part of its function in the cell. What is the big difference in the tertiary structure of the microRNA: MicroRNA tertiary structure?

Hammerhead RNA


Next, let's fold a Hammerhead Ribozyme sequence. This is an RNA made from synthetic RNA but made to fold like a real hammerhead ribozyme. Open the sequence here: Hammerhead Ribozyme

Paste the sequence into the first text box at the RNAfold web-server page.

Next, click Proceed >>

Now let's compare this prediction to the tertiary structure of the Ribonuclease RNA. How is it different? tertiary structure of the Hammerhead RNA.

Telomerase RNA


Next, let's open the telomerase sequence: telomeraseRNA. Telomerase is a complex of RNA and proteins that maintains the ends of chromosomes called "telomeres". Note that this is just a part of the full RNA molecule.

Paste the sequence into the first text box at the RNAfold web-server page.

Next, click Proceed >>

Now let's compare this prediction to the tertiary structure of the telomerase RNA. How is it different? tertiary structure of the telomerase RNA.

tRNA (Transfer RNA)


Next, let's open a tRNA sequence in a new tab: tRNA. This is a tRNA from the bacteria E. coli.

Paste the sequence into the RNAfold web-server, click Proceed >>. What do you notice about its structure that is different from the microRNA?

Now let's compare this prediction to the tertiary structure of the tRNA. How is it different? tertiary structure of the tRNA.


Make a Mutation

Now that you've folded RNA sequences, pick one of these RNAs and choose a location to make a mutation (delete, add or change some nucleotides) that you think will change the structure of the folded RNA. For example, you could change some nucleotides in the microRNA. Paste the RNA sequence you were given into the program NotePad++. Use the "Find" function to locate the place where you want to make your mutation. After mutating your RNA, fold the new sequence and see if the structure has changed.


Bonus Question if you finish early: Given what you've learned about how to work with DNA and RNA sequences, how would you create a perfect hairpin sequence?

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