Translational control of many mRNAs in developing metazoan embryos is achieved 
by alterations in their poly(A) tail length. A family of cytoplasmic 
poly(A)-binding proteins (PABPs) bind the poly(A) tail and can regulate mRNA 
translation and stability. However, despite the extensive biochemical 
characterization of one family member (PABP1), surprisingly little is known 
about their in vivo roles or functional relatedness. Because no information is 
available in vertebrates, we address their biological roles, establishing that 
each of the cytoplasmic PABPs conserved in Xenopus laevis [PABP1, embryonic PABP 
(ePABP), and PABP4] is essential for normal development. Morpholino-mediated 
knockdown of PABP1 or ePABP causes both anterior and posterior phenotypes and 
embryonic lethality. In contrast, depletion of PABP4 results mainly in anterior 
defects and lethality at later stages. Unexpectedly, cross-rescue experiments 
reveal that neither ePABP nor PABP4 can fully rescue PABP1 depletion, 
establishing that PABPs have distinct functions. Comparative analysis of the 
uncharacterized PABP4 with PABP1 and ePABP shows that it shares a 
mechanistically conserved core role in promoting global translation. Consistent 
with this analysis, each morphant displays protein synthesis defects, suggesting 
that their roles in mRNA-specific translational regulation and/or mRNA decay, 
rather than global translation, underlie the functional differences between 
PABPs. Domain-swap experiments reveal that the basis of the functional 
specificity is complex, involving multiple domains of PABPs, and is conferred, 
at least in part, by protein-protein interactions.