Base-pairing between untranslated regions facilitates translation of uncapped, nonpolyadenylated viral RNA

Translationally competent mRNAs form a closed loop via interaction of initiation factors with the 5 ' cap and poly(A) tail. However, many viral mRNAs lack a cap and/or a poly(A) tail. We show that an uncapped, nonpolyadenylated plant viral mRNA forms a closed loop by direct base-pairing (kissing) of a stem loop in the 3 ' untranslated region (UTR) with a stem loop in the 5 ' UTR. This allows a sequence in the 3 ' UTR to confer translation initiation at the 5 ' -proximal AUG. This base-pairing is also required for replication. Unlike other cap-independent translation mechanisms, the ribosome enters at the 5 ' end of the mRNA. This remarkably long-distance base-pairing reveals a novel mechanism of cap-independent translation and means by which mRNA UTRs can communicate.