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. 2004 Aug 6:5:10.
doi: 10.1186/1471-2199-5-10.

Co-transcriptional folding is encoded within RNA genes

Irmtraud M Meyer  1 , István Miklós
Affiliations

Co-transcriptional folding is encoded within RNA genes

Irmtraud M Meyer et al. BMC Mol Biol. .

Abstract

Background: Most of the existing RNA structure prediction programs fold a completely synthesized RNA molecule. However, within the cell, RNA molecules emerge sequentially during the directed process of transcription. Dedicated experiments with individual RNA molecules have shown that RNA folds while it is being transcribed and that its correct folding can also depend on the proper speed of transcription.

Methods: 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.

Results: 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.

Conclusions: These findings have a number of implications for RNA secondary structure prediction methods and the detection of RNA genes.

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Figures

Figure 1
Figure 1
Definition of a competing, alternative helix. Pictorial definition of a competing, alternative helix. The known base-pair between sequence positions i and formula image has to have at least two other directly adjacent base-pairs within the known secondary structure (right) and the competing, alternative helix has to contain an alternative base-pair between sequence positions i and c (c is the competitor of formula image) which has to be contained within a helix of minimum stem length (left).
Figure 2
Figure 2
Definition of the statistics. Pictorial definitions of the four configurations 3'cis, 3'trans, 5'cis and 5'trans which correspond to the four statistics used to measure the directedness of RNA folding. Sequence positions i and formula image form a base-pair within the known secondary structure. Sequence position c is an alternative base-pairing partner for i (but according to the base-pairing rules therefore not for formula image) within a competing, alternative helix of a minimum length minstem. See the text for more explanation.
Figure 3
Figure 3
Distribution of Cis and Trans values. Distribution of Cis and Trans values for the sequences of data sets A and B and both types of weights (plain (p) or free energy based (g)). The area under each curve has been normalized to one to allow a direct comparison between the two data sets.
See this image and copyright information in PMC

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