Edwards et al., Curr Opin Struct Biol 2007

278 Nucleic acids
Figure 4
Foundation. TEE and DJK contributed equally to the writing of this
review.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
of special interest
of outstanding interest
Secondary structure (a) and NMR structure (PDB code 2GIO) (b) of the
ROSE (repressor of heat-shock gene expression) ribosensor, which
functions as an RNA thermometer. Upon increase in temperature (D), a
helix primarily consisting of non-canonical Watson–Crick pairings melts
to liberate a Shine–Dalgarno sequence (depicted in gray boxes). Except
for line drawings, figures were prepared with PyMol [51].
Conclusions
The recent determination of the structures of the metabolite-binding
domains of riboswitches opens the way to
multiple research avenues that take advantage of highresolution
information. These include analysis of the
molecular recognition mechanisms employed by riboswitches
and design of artificial effectors, elucidation of
the mechanism of action of the coenzyme GlcN6P in the
glmS ribozyme and, most generally, coupling of ligandinduced
folding of RNA to the cellular processes of
transcription, post-transcriptional RNA processing and
translation.
Acknowledgements
TEE and DJK are Damon Runyon Fellows, and ARF is a Distinguished
Young Scholar in Medical Research of the WM Keck Foundation.
Supported by grants from the Damon Runyon Cancer Research
Foundation (DRG-1844-04 to TEE and DRG-1863-05 to DJK), the
National Institutes of Health (GM63576 to ARF) and the WM Keck
Current Opinion in Structural Biology 2007, 17:273–279
1. Winkler WC, Breaker RR: Genetic control by metabolite-binding
riboswitches. ChemBioChem 2003, 4:1024-1032.
2. Nudler E, Mironov AS: The riboswitch control of bacterial
metabolism. Trends Biochem Sci 2004, 29:11-17.
3. Winkler WC: Riboswitches and the role of noncoding RNAs
in bacterial metabolic control. Curr Opin Chem Biol 2005,
9:594-602.
4. Tucker BJ, Breaker RR: Riboswitches as versatile gene control
elements. Curr Opin Struct Biol 2005, 15:342-348.
5. Winkler W, Nahvi A, Breaker RR: Thiamine derivatives bind
messenger RNAs directly to regulate bacterial gene
expression. Nature 2002, 419:952-956.
6. Batey RT, Gilbert SD, Montange RK: Structure of a natural
guanine-responsive riboswitch complexed with the
metabolite hypoxanthine. Nature 2004, 432:411-415.
7. Serganov A, Yuan YR, Pikovskaya O, Polonskaia A, Malinina L,
Phan AT, Hobartner C, Micura R, Breaker RR, Patel DJ: Structural
basis for discriminative regulation of gene expression by
adenine- and guanine-sensing mRNAs. Chem Biol 2004,
11:1729-1741.
8. Martick M, Scott WG: Tertiary contacts distant from the
active site prime a ribozyme for catalysis. Cell 2006,
126:309-320.
9.
Thore S, Leibundgut M, Ban N: Structure of the eukaryotic
thiamine pyrophosphate riboswitch with its regulatory ligand.
Science 2006, 312:1208-1211.
The crystal structure of a eukaryotic thi-box riboswitch bound to TPP
reveals bipartate ligand recognition by a pyrophosphate sensor helix and
a pyrimidine sensor helix.
10.
Serganov A, Polonskaia A, Phan AT, Breaker RR, Patel DJ:
Structural basis for gene regulation by a thiamine
pyrophosphate-sensing riboswitch. Nature 2006,
441:1167-1171.
The 2.05 Å crystal structure of a bacterial thi-box riboswitch shows the
TPP–riboswitch interaction in detail. NMR and biochemical analyses of
riboswitch structure and folding are also presented.
11.
Edwards TE, Ferré-D’Amaré AR: Crystal structures of the
thi-box riboswitch bound to thiamine pyrophosphate
analogs reveal adaptive RNA-small molecule recognition.
Structure 2006, 14:1459-1468.
Crystal structures of a bacterial thi-box riboswitch bound to the regulatory
ligand or three different metabolite analogs demonstrate adaptive
recognition of the binding site and correlate affinity with RNA
plasticity.
12. Winkler WC, Nahvi A, Sudarsan N, Barrick JE, Breaker RR: An
mRNA structure that controls gene expression by binding
S-adenosylmethionine. Nat Struct Biol 2003, 10:701-707.
13. Corbino KA, Barrick JE, Lim J, Welz R, Tucker BJ, Puskarz I,
Mandal M, Rudnick ND, Breaker RR: Evidence for a second
class of S-adenosylmethionine riboswitches and other
regulatory RNA motifs in alpha-proteobacteria.
Genome Biol 2005, 6:R70.
14. Fuchs RT, Grundy FJ, Henkin TM: The S(MK) box is a new
SAM-binding RNA for translational regulation of SAM
synthetase. Nat Struct Mol Biol 2006, 13:226-233.
15.
Montange RK, Batey RT: Structure of the S-adenosylmethionine
riboswitch regulatory mRNA element. Nature 2006,
441:1172-1175.
A crystal structure reveals how the class I SAM-responsive riboswitch
recognizes its ligand; this differs from how proteins recognize this ligand.
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