RNA structure: the long and the short of it

Abstract

The database of RNA structure has grown tremendously since the crystal structure analyses of ribosomal subunits in 2000-2001. During the past year, the trend toward determining the structure of large, complex biological RNAs has accelerated, with the analysis of three intact group I introns, A- and B-type ribonuclease P RNAs, a riboswitch-substrate complex and other structures. The growing database of RNA structures, coupled with efforts directed at the standardization of nomenclature and classification of motifs, has resulted in the identification and characterization of numerous RNA secondary and tertiary structure motifs. Because a large proportion of RNA structure can now be shown to be composed of these recurring structural motifs, a view of RNA as a modular structure built from a combination of these building blocks and tertiary linkers is beginning to emerge. At the same time, however, more detailed analysis of water, metal, ligand and protein binding to RNA is revealing the effect of these moieties on folding and structure formation. The balance between the views of RNA structure either as strictly a construct of preformed building blocks linked in a limited number of ways or as a flexible polymer assuming a global fold influenced by its environment will be the focus of current and future RNA structural biology.

Figure 1

Number of RNA structures deposited in the NDB (http://ndbserver.rutgers.edu/) (dark red) and the average number of nucleotides per structure (yellow) given by year. Although the number of structure determinations has grown only slowly, the average structure size has dramatically increased since 2000.

Figure 2

A Watson–Crick base quartet found in a highly conserved region of the SARS virus genome. The quartet is shown in orange, a GNRA-like pentaloop with a closing base pair is in green, a base pair from a second helix at a sharp angle to the tetraloop is shown in magenta and a dinucleotide linker between bases of the quartet is in yellow.

Figure 3

Interacting hairpin loops from the guanine-responsive riboswitch. One loop is in cyan and the other is in magenta, with stacked quartets in the loops colored yellow and orange. Helical stems of the hairpin loops are colored blue.

Figure 4

MMLV core encapsidation signal. Green, GNRA tetraloop; salmon, disordered tetraloop; violet, Watson–Crick double helix; blue, non-canonical base pairs; cyan, base triple; orange, A-minor K-turn; yellow, linker region and bulge base.