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XB-ART-43168
Proc Natl Acad Sci U S A 2011 May 10;10819:7844-9. doi: 10.1073/pnas.1017664108.
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Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development.

Gorgoni B , Richardson WA , Burgess HM , Anderson RC , Wilkie GS , Gautier P , Martins JP , Brook M , Sheets MD , Gray NK .


Abstract
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.

PubMed ID: 21518916
PMC ID: PMC3093506
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a eif4g1 lgals4.2 pabpc1 pabpc1l pabpc4 paip1 pc.1
Morpholinos: pabpc1 MO1 pabpc1 MO2 pabpc1l MO1 pabpc1l MO2 pabpc4 MO1


Article Images: [+] show captions
References [+] :
Belloc, Sequential waves of polyadenylation and deadenylation define a translation circuit that drives meiotic progression. 2008, Pubmed