PABPs [poly(A)-binding proteins] bind to the poly(A) tail of eukaryotic mRNAs and are conserved in species ranging from yeast to human. The prototypical cytoplasmic member, PABP1, is a multifunctional RNA-binding protein with roles in global and mRNA-specific translation and stability, consistent with a function as a central regulator of mRNA fate in the cytoplasm. More limited insight into the molecular functions of other family members is available. However, the consequences of disrupting PABP function in whole organisms is less clear, particularly in vertebrates, and even more so in mammals. In the present review, we discuss current and emerging knowledge with respect to the functions of PABP family members in whole animal studies which, although incomplete, already underlines their biological importance and highlights the need for further intensive research in this area.

Significance: The majority of genes are controlled at the level of mRNA translation, with accurate regulation being critical to cellular function and health. The repression or activation of subsets of mRNAs, so-called “mRNA-specific” regulation, is often mediated by RNA-binding proteins. However, the mechanisms underlying mRNA-specific activation have only been determined in a very few cases. Here, we uncover a mechanism of mRNA-specific activation used by viral and cellular proteins, which share no sequence similarity, suggesting that it may represent a widespread mechanism. Importantly, in so doing, we also expand our knowledge of how two key translation factors, poly(A)-binding protein (PABP) and eukaryotic initiation factor 4G (eIF4G), function during translation initiation, showing they have pleiotropic effects on small ribosomal subunit recruitment.

Aberrant gene expression during gametogenesis is one of the factors underlying infertility, which affects roughly 15% of couples worldwide. Deleted-in-Azoospermia-Like (DAZL), a member of the DAZ-gene family, encodes an mRNA-specific regulator of translation which is essential for gametogenesis in both sexes. In this study we show that DAZL controls gene expression in oocytes by regulating the length of the mRNA poly(A) tail, a major determinant of temporal and amplitudinal gene regulation in germ cells, in which gene expression is regulated entirely post-transcriptionally. We show that DAZL does not induce polyadenylation but that binding of DAZL efficiently inhibits mRNA deadenylation induced by oocyte maturation. We reveal that this activity depends on DAZL-mediated recruitment of poly(A)-binding protein, PABP, to the mRNA. Although DAZL also activates mRNA translation via PABP recruitment, mechanistic analysis revealed that neither translation nor translational activation are required for DAZL to stabilise the poly(A) tail, suggesting two mutually independent posttranscriptional roles for the DAZL-PABP complex. We show that recruited PABP must maintain its ability to bind RNA, leading to a model in which DAZL recruits PABP and/or stabilises PABP binding to poly(A) thereby preventing access of deadenylases. These results indicate that the role of DAZL in regulating germ-cell mRNA fate is more complex than previously thought and inform on the poorly understood links between mRNA translation and deadenylation, showing that they can be mechanistically separable.