The building blocks and motifs of RNA architecture

doi:10.1016/j.sbi.2006.05.009

Current Opinion in Structural Biology

Volume 16, Issue 3, June 2006, Pages 279-287

https://doi.org/10.1016/j.sbi.2006.05.009 Get rights and content

RNA motifs can be defined broadly as recurrent structural elements containing multiple intramolecular RNA–RNA interactions, as observed in atomic-resolution RNA structures. They constitute the modular building blocks of RNA architecture, which is organized hierarchically. Recent work has focused on analyzing RNA backbone conformations to identify, define and search for new instances of recurrent motifs in X-ray structures. One current view asserts that recurrent RNA strand segments with characteristic backbone configurations qualify as independent motifs. Other considerations indicate that, to characterize modular motifs, one must take into account the larger structural context of such strand segments. This follows the biologically relevant motivation, which is to identify RNA structural characteristics that are subject to sequence constraints and that thus relate RNA architectures to sequences.

Introduction

No single definition exists for RNA motifs, as they can be proposed and analyzed at different levels of RNA structure. As discussed in a previous review, RNA motifs can be broadly defined as recurrent structural elements, subject to constraints [1]. This review is complementary to a recent review of new high-resolution RNA structures that exhaustively catalogued new and recurrent motifs [2^••]. Therefore, we do not attempt to comprehensively discuss each newly reported motif, but rather aim to critically review evolving notions of recurrent RNA motifs in the context of RNA function and evolution, and how to identify, find and classify them.

Section snippets

Types of RNA motifs

We can distinguish two main classes of motifs — those that operate at the level of RNA sequence and those that entail a specific three-dimensional (3D) structure, characterized by a set of 3D coordinates. An example of a sequence motif is the Shine–Dalgarno sequence of bacterial mRNAs or the Sm-binding sites of some eukaryotic non-coding RNAs [3]. At an intermediate level of analysis, the secondary structure (2D) of an RNA is prominent because it can be calculated quite accurately from sequence

Secondary structure motifs

How much information can we retrieve from analysis of secondary (2D) structures? Zorn et al. [5] calculate and compare frequency distributions of Watson–Crick (WC) paired nucleotides in helical stems and of nominally unpaired nucleotides in hairpin, internal and junction loops, as they appear in the secondary structures of the 16S and 23S rRNAs. Thus, they treat all bases in ‘loops’ as unpaired, even though a large fraction of them form non-WC base pairs, as is evident from high-resolution 3D

Representations of RNA three-dimensional structure

Different representations can be used to describe molecular structure information [29]. The most basic representation, used by the 3D structure databases, is the Cartesian coordinates of individual atoms, from which other representations can be derived. However, the large number of variables makes the Cartesian representation awkward when comparing structures or searching for recurrent motifs. Internal coordinates (torsion angles) significantly reduce the number of variables and remove the need

Conclusions

Biological data are fundamentally sequence data. Given the ease of obtaining sequence data and the difficulty of determining 3D structures at high resolution, there will always be more sequence data than structural data. The key challenge for RNA structural and computational biologists and bioinformaticians is to fully integrate these two types of data with a common ontology [63]. The fact that structured RNA molecules are mosaics of recurrent modular motifs means that high-resolution 3D

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

NBL acknowledges grant support from the National Institutes of Health (2 R15 GM055898-03) and the American Chemical Society (PRF# 42357 -AC 4).

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View full text

The building blocks and motifs of RNA architecture

Introduction

Section snippets

Types of RNA motifs

Secondary structure motifs

Representations of RNA three-dimensional structure

Conclusions

References and recommended reading

Acknowledgements

Analysis of RNA motifs

Curr Opin Struct Biol

RNA structure: the long and the short of it

Curr Opin Struct Biol

LSm proteins form heptameric rings that bind to RNA via repeating motifs

Trends Biochem Sci

Predictive methods using RNA sequences

Structural motifs in ribosomal RNAs: implications for RNA design and genomics

Biopolymers

The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution

Science

Structures of the bacterial ribosome at 3.5 Å resolution

Science

Structure of the 30S ribosomal subunit

Nature

Structures of helical junctions in nucleic acids

Q Rev Biophys

Topology of three-way junctions in folded RNAs

RNA

RNAMotif, an RNA secondary structure definition and search algorithm

Nucleic Acids Res

Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs

Nucleic Acids Res

Abundance of correctly folded RNA motifs in sequence space, calculated on computational grids

Nucleic Acids Res

Size, constant sequences, and optimal selection

RNA

Finding specific RNA motifs: function in a zeptomole world?

RNA

A graph-topological approach to recognition of pattern and similarity in RNA secondary structures

Biophys Chem

Tree graphs of RNA secondary structures and their comparisons

Comput Biomed Res

Candidates for novel RNA topologies

J Mol Biol

RAG: RNA-as-graphs web resource

BMC Bioinformatics

RAG: RNA-as-graphs database--concepts, analysis, and features

Bioinformatics

Exploring the repertoire of RNA secondary motifs using graph theory; implications for RNA design

Nucleic Acids Res

Classification of non-coding RNA using graph representations of secondary structure

Pac Symp Biocomput

Basis for structural diversity in homologous RNAs

Science

Crystal structure of the specificity domain of ribonuclease P

Nature

Crystal structure of the RNA component of bacterial ribonuclease P

Nature

Structural biology. Evolution of RNA architecture

Science

Frequent occurrence of the T-loop RNA folding motif in ribosomal RNAs

RNA

Motif prediction in ribosomal RNAs lessons and prospects for automated motif prediction in homologous RNA molecules

Biochimie

The influence of different structure representations on the clustering of an RNA nucleotides data set

J Chem Inf Comput Sci

Configurational statistics of polynucleotide chains

Macromolecules

Geometric nomenclature and classification of RNA base pairs

RNA