Current evidence suggests that axonal mRNA transport and local protein synthesis are required for new growth cone formation, retrograde signaling, axon guidance, and elongation ( 1, 2).

The subcellular localization of RNAs has emerged as an important molecular mechanism that is evolutionarily conserved for restricting certain transcripts and proteins to a specific subcellular locale.

On the basis of this work, we propose that ZBP1 and HuD bind to overlapping sites in the β-actin zipcode, but they recognize different features of this target sequence. In contrast, ZBP1 binding to the zipcode RNA depended more on the structural level, as it required the proper spatial organization of a stem-loop that is mainly determined by the U-rich element juxtaposed to the 3′ end of a 5′-ACACCC-3′ motif. HuD showed a binding preference for U-rich sequence. Differences between HuD and ZBP1 were observed in their binding preference to the element. We found that both ZBP1 and HuD bind the zipcode element in rat β-actin mRNA's 3′ UTR. Here we used isolated cis-element sequences of the target mRNA to examine directly protein-RNA interactions in cell-free systems. While HuD possesses three RNA recognition motifs (RRMs), ZBP1 contains two RRMs and four K homology (KH) domains that either increase target specificity or provide a multi-target binding capability.

ZBP1 and HuD are RBPs that play pivotal roles in mRNA transport and local translational control in neuronal processes. Interactions of RNA-binding proteins (RBPs) with their target transcripts are essential for regulating gene expression at the posttranscriptional level including mRNA export/localization, stability, and translation.

Elliott smith either or zip