Protein Aggregation Behavior Regulates Cyclin Transcript Localization and Cell-Cycle Control

Abstract

SUMMARY Little is known about the active positioning of transcripts outside of embryogenesis or highly polarized cells. We show here that a specific G1 cyclin transcript is highly clustered in the cytoplasm of large multinucleate cells. This heterogeneous cyclin transcript localization results from aggregation of an RNA-binding protein, and deletion of a polyglutamine stretch in this protein results in random transcript localization. These multinucleate cells are remarkable in that nuclei cycle asynchronously despite sharing a common cytoplasm. Notably, randomization of cyclin transcript localization significantly diminishes nucleus-to-nucleus differences in the number of mRNAs and synchronizes cell-cycle timing. Thus, nonrandom cyclin transcript localization is important for cell-cycle timing control and arises due to polyQ-dependent behavior of an RNA-binding protein. There is a widespread association between polyQ expansions and RNA-binding motifs, suggesting that this is a broadly exploited mechanism to produce spatially variable transcripts and heterogeneous cell behaviors.

Prions: What Are They Good For?

“…More important is whether a distinct functional consequence can be attributed to the prion-like state. Many cellular proteins form aggregates/oligomers to serve their normal functions (Brangwynne et al 2009, Kwon et al 2013, Lee et al 2013, Malinovska et al 2013, Petrovska et al 2014. Some of the oligomers are stable, though they are not amyloids, whereas other protein assemblies are labile but possess features of amyloids.…”

Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins

“…For example, a prion-like domain of Tia1 targets Tia1 to mammalian stress granules (Gilks et al, 2004). Similarly, P-bodies in yeast assemble through redundant interactions of the Edc3 protein and by a prion domain of Lsm4 (Decker et al, 2007), while an mRNP granule in the fungus Ashbya is driven by a polyQ region in the Whi3 protein (Lee et al, 2013). The P-granules in C. elegans are dependent on the Pgl family of proteins for their assembly, which contain an XFG repeat structure (Updike et al, 2011).…”

Heterochromatin aggregation during DNA elimination in Tetrahymena is facilitated by a prion-like protein

“…Prion-like proteins play important pathological roles in the development of neurodegenerative diseases (Jucker and Walker, 2013), in addition to physiological roles in various biological processes, such as transcriptional regulation for environmental adaptability, translational regulation in the formation of long-term memory and RNA localization in cell cycle regulation (Halfmann et al, 2012;Holmes et al, 2013;Lee et al, 2013;Majumdar et al, 2012;Si et al, 2003). Because heterochromatin bodies are considered nucleoprotein aggregates, we chose to investigate the involvement of a prion-like protein in this process in Tetrahymena.…”