The Unkempt RNA binding protein reveals a local translation program in centriole overduplication.
Abraham MartinezAlexander J Stemm-WolfRyan M SheridanJ Matthew TaliaferroChad G PearsonPublished in: bioRxiv : the preprint server for biology (2024)
Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. Plk4 controls centriole duplication at the heart of centrosome assembly, and elevation of Plk4 promotes centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated Plk4 and find Unkempt, a gene encoding an RNA binding protein with roles in translational regulation, to be one of only two upregulated mRNAs. Unk protein localizes to centrosomes and Cep131-positive centriolar satellites and is required for Plk4-induced centriole overduplication in an RNA-binding dependent manner. Translation is enriched at centrosomes and centriolar satellites with Unk and Cep131 promoting this localized translation. A transient centrosomal downregulation of translation occurs early in Plk4-induced CA. CNOT9, an Unk interactor and component of the translational inhibitory CCR4-NOT complex, localizes to centrosomes at this time. In summary, centriolar satellites and Unk promote local translation as part of a translational program that ensures centriole duplication.
Keyphrases
- binding protein
- cell migration
- nucleic acid
- high glucose
- quality improvement
- diabetic rats
- transcription factor
- heart failure
- gene expression
- stem cells
- drug induced
- endothelial cells
- copy number
- regulatory t cells
- genome wide
- small molecule
- bone marrow
- oxidative stress
- protein kinase
- blood brain barrier
- genome wide identification