Department of Structural Biology, Stanford University School of Medicine, California 94305-5400.
Nature 372: 111-3 (1994)
Abstract
In large structured RNAs, RNA hairpins in which the strands of the
duplex stem are connected by a tetraloop of the consensus sequence
5'-GNRA (where N is any nucleotide, and R is either G or A) are
unusually frequent. In group I introns there is a covariation in
sequence between nucleotides in the third and fourth positions of the
loop with specific distant base pairs in putative RNA duplex stems: GNAA
loops correlate with successive 5'-C-C.G-C base pairs in stems, whereas
GNGA loops correlate with 5'-C-U.G-A. This has led to the suggestion
that GNRA tetraloops may be involved in specific long-range tertiary
interactions, with each A in position 3 or 4 of the loop interacting
with a C-G base pair in the duplex, and G in position 3 interacting with
a U-A base pair. This idea is supported experimentally for the GAAA
loop of the P5b extension of the group I intron of Tetrahymena
thermophila and the L9 GUGA terminal loop of the td intron of
bacteriophage T4 (ref. 4). NMR has revealed the overall structure of the
tetraloop for 12-nucleotide hairpins with GCAA and GAAA loops and
models have been proposed for the interaction of GNRA tetraloops with
base pairs in the minor groove of A-form RNA. Here we describe the
crystal structure of an intermolecular complex between a GAAA tetraloop
and an RNA helix. The interactions we observe correlate with the
specificity of GNRA tetraloops inferred from phylogenetic studies,
suggesting that this complex is a legitimate model for intramolecular
tertiary interactions mediated by GNRA tetraloops in large structured
RNAs.
Mesh Headings
Unique Identifier: 95059379
Chemical Identifiers (Names)