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A Guide to Loop Boosting

An EteRNA Guides Production

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Boosting Defined

  • A term in the game of EteRNA, boosting refers to the placement of bases in a loop, to lower its free energy.

  • Boosting can occur in all types of loops to a limited amount.

  • We'll start out with learning about Internal loops

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Internal Loops

Internal loops are Closed loops (red highlight), with a stack closing it (light blue highlight) on both sides.

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Boosting an internal loop

Free energy of internal loop = 2.3 kcal

Free energy of internal loop boosted = 0.1 kcal

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Boosting an internal loop

As you can see, when boosted, the free energy of the loop on the right is lower, which is GOOD!

Lower Free energy is better.

>

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How to Boost?

What do I do?

?

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How to Boost?

Boosting occurs when there is a G-A mismatch in the loop on the bases next to the stack

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How to Boost?

Closing Base pairs of Loop - Highlighted Blue

Bases next to closing base pair - Highlighted Red

Free Energy - Highlighted Green

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How to Boost?

The G's (circled by Yellow) across from the A's has lowered the free energy to 0.1!

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How to Boost?

The G's (circled by Yellow) across from other G's DOES NOT lower the free energy of the loop - NOT GOOD!

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How to Boost?

Even though we have G across from A, they are not next to the closing base pair, and this does not lower the energy in the loop. NOT GOOD!

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How to Boost Conclusion

What have we learned?

  • Only G (red base) across from A (yellow base) lowers free energy

  • G across from G and A across from A is NOT GOOD (Does not lower free energy)!

  • Only the bases that are next to the closing base pair lower the free energy, changing the rest is not good!

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Types of Internal Loops

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Type 1 Internal Loop - Sym/Asym

  • Can be both Symmetric and Asymmetric
  • Can have a G-A boost on either side, as long as there is a G across from an A in the loop, next to the pair
  • Both sides must be equal or greater than 2 bases in length

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Type 2 - 1-X Asym Loop

  • Boosting is just like regular loops, G across from A
  • Only need one G on the 1 side of 1-X loop
  • Need 2 G's on X side of 1-X loop
  • One side must be only 1 base, and the other side must be 2 or greater

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Type 3 - Bulge Internal Loop, 0-X

  • Only has unpaired bases on one side of the loop.
  • CANNOT BE BOOSTED
  • Boosting only occurs when there is a G across from an A, IN THE LOOP
  • Closing base pairs do not count
  • Best to leave all A's in most circumstances

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Special Loop Circumstances

There are special circumstances and sequences for certain loops. These sequences will not always follow the rules previously described in this presentation, but these sequences will also not apply to any of the previous loop types already stated, being specific to the type of loop.

These loops are the 1-1, 2-2, and 1-2 loop

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Special Loop: 1-1 Loop

As stated previously, G-A mismatches are the best in a loop.

Free Energy = -0.1

However, in 1-1 loops, G-G mismatches are the best.

Free energy = -1.7

WAY BETTER

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Special Loop: 1-1 Loop

So, as a general rule. When you see a 1-1 loop, which is a loop with one free base on each side, use G on both sides for the lowest possible free energy.

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Special Loop: 1-2 Loop

Much like the 1-1 loop, the 1-2 loop can be boosted by a G-G mismatch. On the next page, are some of the better boost options for the 1-2 loop.

A 1-2 Loop is a loop that has 1 free base on one side and 2 free bases on the opposite side.

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1-2 Loop

Each of these are valid boosts

The 2 G's across from the A is typically the best.

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Special Loop: 2-2 Loop

A 2-2 loop is a loop that has 2 bases on each side of the loop

Can be boosted just like any other loop for a bonus in free energy.

This is not the best way to lower the energy (Under most circumstances)

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Special Loop: 2-2 Loop

This is the best way to lower free energy in the 2-2 loop, the tandem UG mismatch

When viewing the numbering of the bases on the RNA, going from lowest to highest, the lowest number must be U, and the highest G.

What happens when you reverse the orientation of the G's and U's?

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Special Loop: 2-2 Loop

As you can see, reversing the orientation of the bases in the loop raises the energy WAY up. This is bad, real bad. Remember, we want the energy in the loop more negative, or lower, and reversing the bases does not do this.

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Thank you for taking your time to watch this presentation, may it have helped in your journey to better your skills in EteRNA.