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FGF2 antiproliferative stimulus triggers proteomic and transcriptional changes associated with nucleolar disorganization in K-ras-driven mouse tumor cells (Nucleoli proteome data)

ABSTRACT: Chromatin plays a crucial role in the intermediation between cell signaling and gene expression. The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has anti-proliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin, nucleolus, and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription regulation, particularly rRNA expression, and chromatin remodeling proteins. Upon 24 hrs of FGF2 stimulation, the global transcriptional rate and nucleolus area increased along with intense nucleolar disorganization detected by fibrillarin dispersion and electron microscopy analyses. We confirmed that FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription regardless of changes in ribosome profiling. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing/modification, since the proteins Nolc1 and Tcof1 were upregulated after FGF2 stimulation. Changes in rRNA expression may be crucial for triggering the antiproliferative effect induced by FGF2 since inhibiting RNA Pol I, responsible for rRNA expression, partially reversed the growth arrest induced by FGF2. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus, directly modulating the proteome of the rDNA loci.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Julia Cunha

LAB HEAD: Julia Pinheiro Chagas da Cunha

PROVIDER: PXD037348 | Pride | 2024-09-28

REPOSITORIES: pride

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			Action	DRS
	Mm_Nucleoli-1_7plex_4hRP_SPS-MS3_Eclipse_2.raw	Raw
	Mm_Nucleoli-2_7plex_4hRP_SPS-MS3_Eclipse_1.raw	Raw
	Mm_Nucleoli-3_7plex_4hRP_SPS-MS3_Eclipse_1.raw	Raw
	Mm_Nucleoli-4_7plex_4hRP_SPS-MS3_Eclipse_1.raw	Raw
	Mm_Nucleoli_7plex_4hRP_SPS-MS3_Eclipse_2020-10-05.msf	Msf

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Project description:The nucleolus is a membraneless organelle responsible for ribosome biogenesis, perinuclear heterochromatin formation, and genome stability regulation. However, how cell fate decision occurs, including early embryonic development, ESC differentiation, and tumorigenesis, remains poorly understood at the nucleolar level. It has been observed that large nucleoli and rDNA hyperactivity are common in pluripotent stem cells and tumor cells, while the nucleolus shrinks and rDNA transcriptional activity decrease during lineage commitment. iPSCs nucleolar size and rDNA transcriptional activity are greater than that before reprogramming. It remains unclear how and when the differentiated cell nucleoli convert to the stem cell nucleoli during iPSC reprogramming.In this study, we found that nucleolar remodeling, manifested as enlarged nucleolus, activation of rDNA transcription, enhanced activity of nucleolar organizing regions (NORs), and conversion of reticular nucleolar ultrastructure into low-granular, is an early and stage-specific event that occurs during iPSCs reprogramming. Our study highlights the importance of rDNA transcriptional activity in the early stages of iPSC reprogramming, which is crucial for nucleolar remodeling and regaining stemness. Interfering rDNA transcription hinders nucleolar remodeling, which has disastrous consequences for chromatin remodeling in early stage of iPSC reprogramming and iPSCs establishment. Moreover, our results revealed a nucleolar regulation on chromatin accessibility during iPSC reprogramming and identified some candidate genes (Mybl2, Bard1 and other chromosome related genes) that might be associated with iPSC reprogramming, which may apply to nucleolar remodeling in other cell fated decision.

Dataset Information

FGF2 antiproliferative stimulus triggers proteomic and transcriptional changes associated with nucleolar disorganization in K-ras-driven mouse tumor cells (Nucleoli proteome data)

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