Fates and functions of RNA-binding proteins under stress.

Exposure to stress activates a well-orchestrated set of changes in gene expression programs that allow the cell to cope with and adapt to the stress, or undergo programmed cell death. RNA-protein interactions, mediating all aspects of post-transcriptional regulation of gene expression, play crucial roles in cellular stress responses. RNA-binding proteins (RBPs), which interact with sequence/structural elements in RNAs to control the steps of RNA metabolism, have therefore emerged as central regulators of post-transcriptional responses to stress.

An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock.

Post-transcriptional regulation by RNA-binding proteins (RBPs) is a major mode of controlling gene expression under stress conditions. The RBP HuR regulates the translation/turnover of multiple mRNAs in stress responses. HuR is degraded in response to heat stress consequent to ubiquitination of the K182 amino acid residue.

Cooperation and competition by RNA-binding proteins in cancer.

Post-transcriptional regulation of gene expression plays a major role in determining the cellular proteome in health and disease. Post-transcriptional control mechanisms are disrupted in many cancers, contributing to multiple processes of tumorigenesis. RNA-binding proteins (RBPs), the main post-transcriptional regulators, often show altered expression and activity in cancer cells.

Negative feedback regulation by HuR controls TRIM21 expression and function in response to UV radiation.

The E3 ubiquitin ligase TRIM21 plays a crucial role as a negative regulator of innate immune responses. Recent evidence has also indicated the involvement of TRIM21 in the genotoxic stress response and suppressing tumorigenesis. Our previous work has demonstrated a new function of TRIM21 in inhibiting p53 protein synthesis by degrading the RNA-binding protein HuR in response to UV radiation.