The Poly(C) binding protein Pcbp2, and its retrotransposed derivative Pcbp1, are independently essential to mouse development. Mus musculus

RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp’s (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome. Overall design: mRNA-seq on fetal liver tissue from 12.5 days post coitum. 4 replicates of WT and 3 replicates of PCBP2 Knockout

RNA结合蛋白（RNA-binding proteins）参与一系列复杂的转录后调控过程，这类调控对细胞类型特化与体细胞发育至关重要。尽管学界已对这类蛋白完成了详尽的生化表征，但每种RNA结合蛋白对哺乳动物胚胎发育的具体影响程度仍未完全阐明，且这类蛋白亚群间的功能冗余水平仍有待商榷。多聚(C)结合蛋白（poly-(C) binding proteins，即Pcbps、aCPs与hnRNPEs）由一个高度保守且广泛表达的基因家族编码。该家族的两个主要同工型Pcbp2与Pcbp1可在多种组织中稳定表达，并在细胞核与细胞质层面共同调控基因表达。本研究发现，Pcbp1基因敲除胚胎会在植入着床阶段丧失生存能力。与之相反，Pcbp2基因敲除胚胎可存活至妊娠中期，随后因心血管与造血系统异常而出现生存能力下降。分别携带Pcbp1或Pcbp2敲除等位基因的成年杂合小鼠，仅表现出轻度且无显著影响的生长缺陷。上述结果表明，Pcbp1与Pcbp2分别是小鼠胚胎发育及出生后生长所必需的基因；同时揭示了Pcbp2在造血过程中发挥非冗余的体内功能，并为“由Pcbp2经逆转录转座衍生而来的Pcbp1已在哺乳动物基因组中演化出必需功能”这一论点提供了直接证据。实验设计：对妊娠第12.5天的胎肝组织开展mRNA测序（mRNA-seq），其中野生型（WT）样本设置4个生物学重复，PCBP2敲除样本设置3个生物学重复。