Template-based prediction of ribosomal RNA secondary structure

Abstract

Determining the structure of ribosomal RNAs (rRNAs) is one of the crucial steps in understanding the process of protein synthesis, for which rRNAs are one of the basic components. Nevertheless, due to extreme technical difficulties, spatial (3D) structures have been resolved experimentally for only 14 organisms. Also, computational prediction of 3D rRNA structure is almost impossible, and prediction of secondary structure (the list of base pairs in the folded RNA), an important intermediate step between sequence and 3D structure that is used broadly in modeling of RNA structures, is in the case of rRNAs hindered by both extreme sequence length and high structure complexity. Here we present a proof-of-concept for an rRNA secondary structure prediction method that utilizes known structures as structural templates. Our template-based prediction algorithm determines those regions of the sequence for which structure is being predicted that are conserved well enough so that their secondary structure can be copied over from the template. The structure of the remaining, unconserved regions is predicted using a thermodynamic folding model. Applying a baseline implementation of our algorithm to the E. coli 16S rRNA, we have achieved state-of-the-art recall and precision using the structure of T. thermophilus 16S rRNA as a template.