eIF4G2 balances its own mRNA translation via a PCBP2-based feedback loop.

Poly(rC)-binding protein 2 (PCBP2, hnRNP E2) is one of the most abundant RNA-binding proteins in mammalian cells. In humans, it exists in seven isoforms, which are assumed to play similar roles in cells. The protein is shown to bind 3' untranslated regions (3' UTRs) of many mRNAs and regulate their translation and/or stability, but nothing is known about functional consequences of PCBP2 binding to 5' UTRs. Here we show that the PCBP2 isoform f interacts with the 5' UTRs of mRNAs encoding eIF4G2 (a translation initiation factor with yet unknown mechanism of action, also known as DAP5) and Cyclin I, and inhibits their translation in vitro and in cultured cells, while the PCBP2 isoform e only affects Cyclin I translation. Furthermore, eIF4G2 participates in a cap-dependent translation of the PCBP2 mRNA. Thus, PCBP2 and eIF4G2 seem to regulate one another's expression via a novel type of feedback loop formed by the translation initiation factor and the RNA-binding protein.