Folding of rna-dna hybrid molecules ?

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2dim
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Joined: 07/18/2011

First of all I was going to thank for making mfold available over the website. I have been using the program in analyses of possible structures of viruses and related molecules. Provided the interests focus on specific group of reverse transcribing elements , I came up with the specific question , I thought I would share. Presently the server offers separate forms for folding the RNA and DNA. While it is clearly 'demand driven concept' the molecules involved in the replication of the group of retroviruses do include RNA-DNA hybrids such us primer tRNA::cDNA 5'3' hybrid molecule. Provided above I started to wonder if perhaps it wouldn't be impossible to formulate a merge RNA-DNA folding form able to fold possible structures and evaluate the energies?

Wadim

malim
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Joined: 08/27/2011
A technique is described for

A technique is described for forming molecular hybrids between RNA in solution and the DNA of intact cytological preparations.

zukerm
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Joined: 11/12/2010
DNA and RNA together

An excellent suggestion. I've been thinking about this problem for almost 25 years. First of all, let's distinguish between folding a chimeric molecule, where ribonucleotides and deoxyribonucleotides are mixed in a single linear polymer, and hybridizing an RNA molecule with a DNA molecule, which I think is what you want. Perhaps the time has come to create a program and web server to solve the second, easier problem. I invite you to look at the work of Naoki Sugimoto at Konan University. I met him in 1986 when he had just started working on deriving free energy parameters for hybridizing RNA with DNA. You can find him here. It is easy to find his publications. In the past, the problem in using his parameters was that they were only for perfect or almost perfect hybridization between an RNA and a DNA of the same length. That was true over a decade ago, so maybe the situation is changed. Also, the development of the UNAFold software and DINAMelt web server have altered the situation. His parameters could be used as one of the options on the DINAMelt web server. Folding a chimeric molecule would be much more difficult, mainly because of a lack of free energy parameters for such molecules. I'm glad that you wrote and caused me to reexamine this matter.