Our overall goal is to understand the mechanisms controlling mRNA turnover and the relationships between mRNA stability, localization, and cellular stress pathways. We are currently focused on how cells employ mRNA decay in regulating endoplasmic reticulum (ER) function. As the entry point for the secretory pathway, the ER is responsible for folding and processing an enormous flux of proteins, yet it must maintain a strict quality control system to ensure that misfolded proteins do not move to the cell surface. Disruption in the balance between incoming proteins and the folding capacity of the ER, termed ER stress, occurs in many human diseases and is counteracted by a collection of stress response pathways. One such pathway, which we call Regulated Ire1-dependent Decay (RIDD), initiates the rapid and widespread degradation of mRNAs associated with the ER membrane. RIDD has the potential both to immediately relieve the burden on the ER (by destroying the templates for proteins that are processed in the ER) and to clear out translocation and folding machinery to accommodate new translation of important ER-associated factors. We are investigating the mechanism and specificity of this pathway and its role in physiological stress.
- Molecular biology of the cell
- mRNA decay
- endoplasmic reticulum function
- stress responses
- Bae D, Moore K, Mella J, Hayashi S, Hollien J. Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress. Journal of Cell Biology. 2019. 218(4): 1118-1127.
- Lee JE, Morrison W, Hollien J. Hairy and enhancer of split 1 (HES1) protects cells from endoplasmic reticulum stress-induced apoptosis through repression of GADD34. Journal of Biological Chemistry. 2018. Apr 20;293(16):5947-5955. doi 10.1074/jbc.RA118.002124.
- Nelson J, Moore KA, Chapin A, Hollien J, Metzstein MM. Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability. eLife 2016. 10.7554/eLife.12876
- Moore K, Hollien J. Ire1-mediated decay in mammalian cells relies on mRNA sequence, structure, and translational status. Mol Biol Cell. 2015. 26(16):2873-84.
- Lee JE, Oney M, Frizzel K, Phadnis N, and Hollien J. Drosophila melanogaster Activating transcription factor 4 Regulates Glycolysis during Endoplasmic Reticulum Stress. G3. 2015. 5(4): 667-75.
- Sharma AK, Plant JJ, Rangel AE, Meek KN, Anamisis AJ, Hollien J, Heemstra JM. Fluorescent RNA labeling using self-alkylating ribozymes. ACS Chem Biol. 2014. 9(8):1680-4.
- Gaddam D, Stevens N, Hollien J. Comparison of mRNA localization and regulation during endoplasmic reticulum stress in Drosophila cells. Mol Biol Cell. 2013. 24(1):14-20. PMCID: 3530775.
- Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol. 2009. 186(3):323-31. PMCID: 2728407.
- Hollien J, Weissman JS. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science. 2006. 313(5783):104-7.
- Biol 5120: Gene Expression