IGF2BP3 regulates RNA metabolism during unfolded protein response [PAR-CLIP]

The Unfolded Protein Response (UPR) is a highly conserved signaling cascade that maintains ER homeostasis. While the transcriptional response is paramount for UPR signaling, several mRNAs are regulated at the posttranscriptional level, yet how this is achieved remains poorly understood.

Here, we show that a highly conserved RNA-binding protein, IGF2BP3, interacts with transcripts encoding for the UPR target genes and regulates the UPR signaling. During ER stress, IGF2BP3 destabilized most of its targets, including the UPR target RNAs. On the other hand, IGF2BP3 stabilized a subset of mRNAs encoding for transcription regulators through this indirectly regulated transcription of the UPR target genes.