New in silico approach to assessing RNA secondary structures with non-canonical base pairs.

Ryszard Adamiak,Maciej Antczak,Agnieszka Rybarczyk,Natalia Szostak,Tomasz Zok,Marta Szachniuk,Mariusz Popenda,Jacek Blazewicz

doi:10.1186/s12859-015-0718-6

Abstract

BackgroundThe function of RNA is strongly dependent on its structure, so an appropriate recognition of this structure, on every level of organization, is of great importance. One particular concern is the assessment of base-base interactions, described as the secondary structure, the knowledge of which greatly facilitates an interpretation of RNA function and allows for structure analysis on the tertiary level. The RNA secondary structure can be predicted from a sequence using in silico methods often adjusted with experimental data, or assessed from 3D structure atom coordinates. Computational approaches typically consider only canonical, Watson-Crick and wobble base pairs. Handling of non-canonical interactions, important for a full description of RNA structure, is still very difficult.ResultsWe introduce our novel approach to assessing an extended RNA secondary structure, which characterizes both canonical and non-canonical base pairs, along with their type classification. It is based on predicting the RNA 3D structure from a user-provided sequence or a secondary structure that only describes canonical base pairs, and then deriving the extended secondary structure from atom coordinates. In our example implementation, this was achieved by integrating the functionality of two fully automated, high fidelity methods in a computational pipeline: RNAComposer for the 3D RNA structure prediction and RNApdbee for base-pair annotation.ConclusionsThe presented methodology ties together existing applications for RNA 3D structure prediction and base-pair annotation. The example performance, applying RNAComposer and RNApdbee, reveals better accuracy in non-canonical base pair assessment than the compared methods that directly predict RNA secondary structure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0718-6) contains supplementary material, which is available to authorized users.

Highlights

The function of RNA is strongly dependent on its structure, so an appropriate recognition of this structure, on every level of organization, is of great importance
We have demonstrated a novel approach for the automated assessment of extended RNA secondary structure from sequence or secondary structure
It is founded on the concept of annotating the extended RNA secondary structure on the tertiary coordinates, predicted in the preliminary step

Summary

Introduction

The function of RNA is strongly dependent on its structure, so an appropriate recognition of this structure, on every level of organization, is of great importance. RNA molecules play an important role in many cellular processes, serving as the carriers of genetic information but participating in the regulation of gene expression and acting as catalysts in many biological pathways [1] These functions result from the sequence and the three-dimensional (3D) shape assumed by the molecule [2]. A classical approximation of the secondary structure considers Watson-Crick AU and GC base pairs, as well as wobble pairs These three types, regarded as canonical, are the stabilizing factors in the RNA folding process. A deep investigation into RNA tertiary interactions, made possible due to the growing number of known RNA 3D structures, revealed a great diversity of other base-base interactions They are referred to as non-canonical and often defined as neither Watson-Crick (non W-C) nor wobble

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Results

Conclusion