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

•Whi3 RNA-binding proteins cluster CLN3 transcripts to pattern the Ashbya syncytium•Cyclin transcript clustering requires a polyQ region in Whi3•Local differences in cyclin transcript clustering control nuclear cell-cycle times•Thus, polyQ clustering of RNA-binding proteins can spatially pattern mRNA function

SummaryLittle 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.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (2884 K)

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