Huge thank you to our collaborators, Ameres @ameressl.bsky.social and Versteeg labs, for their essential input, insights, and support!

6/ 📜 Check out the full study for details!
www.biorxiv.org/content/10.1...

@gekaragoz.bsky.social @maxperutzlabs.bsky.social @vbcscitraining.bsky.social
#RNA #UPR #ERstress #IGF2BP3 #RBP

5/ 🏥 Why does this matter? The UPR is implicated in development and cancer - contexts where IGF2BP3 is highly expressed. This dual-layered regulatory mechanism may allow cells to shift between opposing IGF2BP3 functions, enabling cell state-specific fate decisions.

4/ 🔬 Mechanistically, we observed increased association of IGF2BP3 with the mRNA decapping complex during ER stress, which can result in enhanced degradation of IGF2BP3 targets

3/📉 By tracking changes in total and newly transcribed mRNAs, we show that IGF2BP3 facilitates UPR via two distinct mechanisms:
• It reduces protein folding load by destabilizing most of its target mRNAs
• It upregulates UPR effectors stabilizing mRNAs encoding select transcriptional regulators

2/🔬 IGF2BP3 is an RNA-binding protein known for regulating mRNA stability, particularly in development & cancer. Surprisingly, under ER stress, IGF2BP3 binds key UPR effector transcripts including XBP1, HSPA5, and DDIT3 (CHOP) —major regulators of ER stress adaptation & apoptosis