Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome.
Proc Natl Acad Sci U S A,
PubMed id: 21245352
Internal ribosome entry site (IRES) RNAs are elements of viral or cellular mRNAs
that bypass steps of canonical eukaryotic cap-dependent translation initiation.
Understanding of the structural basis of IRES mechanisms is limited, partially
due to a lack of high-resolution structures of IRES RNAs bound to their cellular
targets. Prompted by the universal phylogenetic conservation of the ribosomal P
site, we solved the crystal structures of proposed P site binding domains from
two intergenic region IRES RNAs bound to bacterial 70S ribosomes. The structures
show that these IRES domains nearly perfectly mimic a tRNA • mRNA interaction.
However, there are clear differences in the global shape and position of this
IRES domain in the intersubunit space compared to those of tRNA, supporting a
mechanism for IRES action that invokes hybrid state mimicry to drive a
noncanonical mode of translocation. These structures suggest how relatively
small structured RNAs can manipulate complex biological machines.