Mutational Effects In Trna

Question

[Raghul]

Hi

It was easy to learn the possible mutational effects for protein with so much literature available. My case becomes difficult as it happens in mitochondrial tRNA. How can I predict the effects of mutation in a tRNA in positions which are not "active sites"? For eg a mutation in a stem region of T-arm where no enzyme interacts. There are tools like Vienna RNAfold, RPI mfold server but how can I use them ? What are the parameters to check whether the mutation alters the stability of the structure or that affects the stability in nearby region etc.

We also have this situation for tRNA- if we have leu-tRNA sequence and predict tRNA from available programs we may not get the accurate structure that is published.This is not the case for protein structure, if there is homology the protein modeling tools give the most possible accurate structure!

thank you

raghul

Answer 1

[Michael]

It is surprising that you write "we may not get the accurate structure that is published". I think that might be for the reason that you are using the wrong tools as tRNA prediction is possibly the best and most accurately solved prediction problem in bioinformatics. "Standard" RNAfolding tools do not perform well on tRNA (my experience). Have a look at tRNAScan-SE, you could scan your mutated sequence and compare to the original. However, a single mutated tRNA will most likely not yield a phenotype even when totally dysfunctional, because of multiple copies of tRNAs of the same type in the genome.

[Raghul]

Thank you. Whatever told by you was correct. Sometimes "odd" things happen & I highlighted them wrongly as common! sorry for that!

For eg I took a tRNA gene sequence separately & did a prediction with tRNAScan-SE and it told nothing could be predicted.

Then I got results with Aragorn (ARWEN).

An odd event-For a ser-tRNA sequence Aragorn predicted an extra pair in acceptor stem

All this confusion could be due to my poor knowledge about how the software works!

A single mutated tRNA will yield a different phenotype in Humans if it is from mitochondria, mostly. The phenotype could be with varying degrees of Penetrance & Expressivity (Conditions apply!)

[Michael]

I think you should compare the output of both tools by plotting the predicted structure. I'd probably still stick with tRNAScan-SE because it has higher specificity than Aragorn at comparable sensitivity (despite Aragorn's increased speed which possibly is not relevant). As with your argument towards tRNAs in mitochondria (which I initially overlooked in you question), it sounds plausible, because there are less copies of tRNA in the mitochondrial genome, but I don't have the knowledge to judge this I suppose. Maybe I should have read: http://www.ncbi.nlm.nih.gov/pubmed/21935892

[Michael]

Maybe you could post the outcome of both predictions?