Microtubule-based mRNA transport is widely used to restrict protein expression
to specific regions in the cell and has important roles in defining cell
polarity and axis determination as well as in neuronal function. However, the
structural basis of recognition of cis-acting mRNA localization signals by motor
complexes is poorly understood. We have used NMR spectroscopy to describe the
first tertiary structure to our knowledge of an RNA element responsible for mRNA
transport. The Drosophila melanogaster fs(1)K10 signal, which mediates transport
by the dynein motor, forms a stem loop with two double-stranded RNA helices
adopting an unusual A'-form conformation with widened major grooves reminiscent
of those in B-form DNA. Structure determination of four mutant RNAs and
extensive functional assays in Drosophila embryos indicate that the two
spatially registered A'-form helices represent critical recognition sites for
the transport machinery. Our study provides insights into the basis for RNA
cargo recognition and reveals a key biological function encoded by A'-form RNA
conformation.
