Exercise 1 - RNA-RNA interaction

So far, we discussed regulatory mechanisms how ncRNAs can hinder translation of mRNAs. Develop some hypotheses how ncRNAs can regulate via RNA-RNA interaction other ncRNAs, which are not translated.

Hide
Solution
  1. trigger decay due to binding (similar to to mRNA decay)
  2. block functional binding site (i.e. hinder their functional binding)
  3. trigger refolding via RRI, which blocks or opens functional site of target
  4. \(\cdots\)

Exercise 2 - Hybridization-focused RRI prediction

2.1

When do we stop the traceback of hybridization-focused RRI prediction when using the introduced recursions for energy minimization based on the Nearest-Neighbor model?

Hide
Solution

When we encounter a cell value equal to \(eInit\), which represents the left-most RRI base pair.

2.2

Is the traceback end from the last question unique? That is, are we sure that the traceback ends at this point? What is the consequence?

Hide
Solution

No, it might be that the overall RRI energy including bulges equals \(eInit\), such that two recursion cases provide the same energy. Thus, the interaction length depends on the case order within the recursion. If we first test for \(eInit\), we will always get the shorter RRI (which is preferred), otherwise the longer one.

2.3

For local alignment, we know of so called mosaic effects, ie. long local alignment with low score are eventually a combination of some short, compact subalignments connected by badly scored parts of low sequence similarity. Since hybridization-focused RRI prediction is technically similar, do you expect similar effects as well or are such cases prevented?

Hide
Solution

Same problem holds for hybrid-only RRI prediction, since we also have a summation-based scoring. That is, as long as the overall score stays below \(eInit\), intermediate bad sub-RRIs can be accumulated to bridge between compact and stable RRI helices.

Exercise 3 - Generalized RRI prediction

3.1

Draw at least 3 sketches of RNA-RNA interactions (without sequence details) consisting of intra- and inter-molecular base pairing that can be produced via a traceback based on the introduced IRIS recursion.

Hide
Solution

3.2

Find two RRIs consisting of intra- and inter-molecular base pairs (without sequence details) that cannot be decomposed/modeled by the introduced IRIS recursion.

Hide
Solution

3.3

Draw a Feynman diagram for the following RNA-RNA interaction. Decide whether this RRI can be modeled using the IRIS recursion. If yes, indicate a possible decomposition order, otherwise highlight the structural parts that make it impossible to decompose.

Hide
Solution