%0 Journal Article
%T Co-transcriptional folding is encoded within RNA genes
%A Irmtraud M Meyer
%A Istv¨˘n Mikl¨Žs
%J BMC Molecular Biology
%D 2004
%I BioMed Central
%R 10.1186/1471-2199-5-10
%X The main aim of this work is to study if and how co-transcriptional folding is encoded within the primary and secondary structure of RNA genes. In order to achieve this, we study the known primary and secondary structures of a comprehensive data set of 361 RNA genes as well as a set of 48 RNA sequences that are known to differ from the originally transcribed sequence units. We detect co-transcriptional folding by defining two measures of directedness which quantify the extend of asymmetry between alternative helices that lie 5' and those that lie 3' of the known helices with which they compete.We show with statistical significance that co-transcriptional folding strongly influences RNA sequences in two ways: (1) alternative helices that would compete with the formation of the functional structure during co-transcriptional folding are suppressed and (2) the formation of transient structures which may serve as guidelines for the co-transcriptional folding pathway is encouraged.These findings have a number of implications for RNA secondary structure prediction methods and the detection of RNA genes.Most of the existing computational methods for RNA secondary structure prediction fold an already completely synthesized RNA molecule. This is done either by minimizing its free energy (e.g. done by MFOLD [1-3] and by the programs of the VIENNA package [4-8]) or by maximizing the probability under a model whose parameters can incorporate a variety of different sources of information, e.g. comparative information, free energy and evolutionary information (e.g. [9], TRNASCAN-SE [10], PFOLD [11,12] and QRNA [13]). All of these programs, including those that predict folding pathways by folding an already synthesized RNA sequence [14,15], therefore disregard the effects that co-transcriptional folding may have on the RNA's functional secondary structure. They essentially aim to predict the thermodynamic RNA structure, i.e. the secondary structure that minimizes the free energy of
%U http://www.biomedcentral.com/1471-2199/5/10