Sequence-specific RNA binding by Bicoid

It has recently been reported that the bicoid protein (Bcd), a homeodomain-containing protein which forms an anterior-to-posterior gradient during early Drosophila embryogenesis, can bind messenger RNA encoding the caudal protein (Cad) and repress its translation1,2. This may be mediated by direct interactions between the homeodomain and a discrete RNA sequence in the untranslated 3′ region of the cad transcript, the Bcd response element(BRE)1,2. The evidence for direct and specific homeodomain-RNA interactions depends principally on the results of competition experiments1 but these could not be reproduced under the conditions originally reported3. Here we present competition experiments performed under different conditions confirming that direct, sequence-specific interactions can occur between the Bcd homeodomain and the cad BRE. We also extend previous evidence1 that site-specific RNA binding by the Bcd homeodomain depends on the lysine at position 9 of helix III, an amino-acid that mediates site-specific DNA binding4,5,6.