Membrane and signalling molecules are produced in a cellular compartment called the
endoplasmic reticulum (ER). When this process goes wrong a situation known as ER stress
cells activate a protective system called the unfolded protein response (UPR). The UPR
restores balance by adjusting gene expression. While much is known about how this works at the
level of gene expression, we know far less about what happens after messenger RNAs (mRNAs)
the molecules that carry genetic instructions to make proteins are produced. These post-
transcriptional processes play a key role in rapidly adjusting protein synthesis during stress and
are essential for maintaining cell viability.
Our recent work uncovered a key player in this process: a protein called IGF2BP3. This RNA-
binding protein binds to the mRNAs of genes involved in the UPR, influencing the levels of those
messengers. Under normal conditions, IGF2BP3 helps protect these mRNAs. However, during
ER stress, its behavior changes instead of stabilizing mRNAs, it promotes their breakdown.
The mechanism by which this switch occurs is still a mystery. This project aims to elucidate
precisely how these molecular changes affect IGF2BP3s activity and, in turn, how cells fine-tune
gene expression during stressa process essential for cell survival.
IGF2BP proteins are often overproduced in aggressive cancers. Understanding how IGF2BP3
regulates mRNAs during ER stress will not only shed light on a fundamental process in cell biology
but also help explain how tumors exploit stress responses to grow and survive.