Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mol Cell Biol. 2014 Apr;34(7):1300-9. doi: 10.1128/MCB.01683-13. Epub 2014 Jan 27.
The expression of an mRNA is strongly impacted by its 3' poly(A) tail and associated poly(A)-binding proteins (PABPs). Vertebrates encode six PABP isoforms that vary in abundance, distribution, developmental control, and subcellular localization. Here we demonstrate that the minor PABP isoform PABPC4 is expressed in erythroid cells and impacts the steady-state expression of a subset of erythroid mRNAs. Motif analyses reveal a high-value AU-rich motif in the 3' untranslated regions (UTRs) of PABPC4-impacted mRNAs. This motif enhances the association of PABPC4 with mRNAs containing critically shortened poly(A) tails. This association may serve to protect a subset of mRNAs from accelerated decay. Finally, we demonstrate that selective depletion of PABPC4 in an erythroblast cell line inhibits terminal erythroid maturation with corresponding alterations in the erythroid gene expression. These observations lead us to conclude that PABPC4 plays an essential role in posttranscriptional control of a major developmental pathway.
mRNA 的表达受到其 3' 聚（A）尾和相关的多聚（A）结合蛋白（PABP）的强烈影响。脊椎动物编码六种 PABP 同工型，其丰度、分布、发育调控和亚细胞定位存在差异。在这里，我们证明了次要的 PABP 同工型 PABPC4 在红细胞中表达，并影响一组红细胞 mRNA 的稳态表达。基序分析揭示了 PABPC4 影响的 mRNA 的 3' 非翻译区（UTR）中存在一个高价值的富含 AU 的基序。该基序增强了 PABPC4 与含有严重缩短的聚（A）尾的 mRNA 的结合。这种结合可能有助于保护一组 mRNA 免受加速降解。最后，我们证明了在红细胞母细胞系中选择性耗尽 PABPC4 会抑制终末红细胞成熟，并相应改变红细胞基因表达。这些观察结果使我们得出结论，PABPC4 在主要发育途径的转录后控制中发挥着重要作用。
