Researchers from the University of Illinois School of Molecular & Cellular Biology are examining the influence on nuclear pathways from the molecular chaperone, TCP-1 Ring complex (TRiC).
Cell and developmental biology professor Brian Freeman’s lab focuses on chaperonins like TRiC, which help fold proteins and assemble protein complexes. In their newest publication, the Freeman lab uncovered the connection between TRiC and RNA polymerase II — a relationship that could provide insights into disease mechanisms with potential implications for patient care.
Their findings were recently published in Molecular Cell.
Scientists have known that cytoplasmic TRiC helps with the maturation of new polypeptides, but this new research shows how it directly regulates RNA polymerase II activity in addition to its regular homeostatic activity and presence in the nucleus.
“We had the phenotype that when the chaperonin is mutated, transcription changed a lot. But there wasn’t an answer as to exactly how that happens,” said Anusmita Biswas, a PhD student in the Freeman lab. “Then I did further experiments to show if the RNA Polymerase II binding was directly correlated to transcription. It turns out that greater chaperonin binding increased transcription and the inverse suppressed transcription.”
Using sequencing, biochemical techniques, and microscopy, the Freeman lab was able to determine a clear relationship between the TRiC chaperonin and RNA polymerase II. However, the role of TRiC is still not fully understood, and researchers are just beginning to uncover the many ways this chaperonin influences nuclear components within the cell.
“I hope this paper expands science’s view of chaperonin’s away from just nascent protein folding,” said Biswas. “The chaperonin actually sits in the nucleus, working with mature peptides and completely formed complexes that can completely change their activity. This provides a demonstration of cytosolic chaperonin in the nucleus, mediating polymerase transcription, and acting as a link between the cytosol and nucleus.”
TRiC dysregulation has been associated with several human diseases, including cancer, neurodegenerative disorders, myocardial infarction, and Down syndrome. Further studies investigating the three-dimensional structure and molecular mechanism behind the TRiC chaperonin’s interaction with RNA polymerase would provide greater insight into this protein's function and its role in human health and disease.
