Mammalian PABPC4 is non-essential, but has roles in growth, post-natal survival and haematopoiesis

Cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins which play crucial roles in mRNA translation and stability. In mammals, two family members, PABPC1 and PABPC4 appear widely expressed, but the consequences of their loss of function in vivo remain unknown. Unexpectedly, we reveal that mammalian PABPC4 is not essential for development, contrary to findings in non-mammalian vertebrates. However, its loss affects birth weight, post-natal growth trajectories and survival although these were not tightly associated. Growth to adulthood was impacted in a sexually dimorphic manner. Viable PABPC4-deficient mice allowed us to test the hypothesis that it is required for haemoglobin synthesis within red blood cells. Surprisingly, we find that PABPC4 loss leads to microcytic red blood cells, but not reduced haemoglobin levels, and conditional genetic approaches established that this was not a red blood cell intrinsic effect. These results challenge previous findings from cell-based models. This work provides the first insights into the biological functions of mammalian PABPC4, and caution against inferring mammalian PABPC function from work in cell-based models and/or non-mammalian species.