E2F1 and RNA binding protein QKI comprise a negative feedback in the cell cycle regulation

Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful model for how, when, and where specific identities are established for condensates. We identified residues on Whi3 that are differentially phosphorylated under specific conditions and generated mutants that ablate this regulation. This yielded separation of function alleles that were functional for either cell polarity or nuclear cycling but not both. This study shows that phosphorylation of individual residues on molecules in biomolecular condensates can provide specificity that gives rise to distinct functional identities in the same cell.

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RPSAP52 lncRNA Inhibits p21Waf1/CIP Expression by Interacting With the RNA Binding Protein HuR

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504019x15761465603129 ◽

2020 ◽

Vol 28 (2) ◽

pp. 191-201

Author(s):

Daniela D’Angelo ◽

Claudio Arra ◽

Alfredo Fusco

Keyword(s):

Cell Cycle ◽

Pituitary Adenomas ◽

Noncoding Rna ◽

Rna Binding ◽

Kinase Inhibitor ◽

Cell Transformation ◽

Binding Protein ◽

Critical Role ◽

Rna Binding Protein ◽

Messenger Rnas

Long noncoding RNAs have been recently demonstrated to have an important role in fundamental biological processes, and their deregulated expression has been found in several human neoplasias. Our group has recently reported a drastic overexpression of the long noncoding RNA (lncRNA) RPSAP52 (ribosomal protein SA pseudogene 52) in pituitary adenomas. We have shown that this lncRNA increased cell proliferation by upregulating the expression of the chromatinic proteins HMGA1 and HMGA2, functioning as a competing endogenous RNA (ceRNA) through competitively binding to microRNA-15a (miR-15a), miR-15b, and miR-16. The aim of this work was to identify further mechanisms by which RPSAP52 overexpression could contribute to the development of pituitary adenomas. We investigated the involvement of RPSAP52 in the modulation of the expression of cell cycle-related genes, such as p21Waf1/CIP, whose deregulation plays a critical role in pituitary cell transformation. We report that RPSAP52, interacting with the RNA binding protein HuR (human antigen R), favors the delocalization of miR-15a, miR-15b, and miR-16 on the cyclin-dependent kinase inhibitor p21Waf1/CIP1 that, accordingly, results in downregulation in pituitary adenomas. A RNA immunoprecipitation sequencing (RIPseq) analysis performed on cells overexpressing RPSAP52 identified 40 messenger RNAs (mRNAs) enriched in Argonaute 2 (AGO2) immunoprecipitated samples. Among them, we focused on GAS8 (growth arrest-specific protein 8) gene. Consistently, GAS8 expression was downregulated in all the analyzed pituitary adenomas with respect to normal pituitary and in RPSAP52-overepressing cells, supporting the role of RPSAP52 in addressing genes involved in growth inhibition and cell cycle arrest to miRNA-induced degradation. This study unveils another RPSAP52-mediated molecular mechanism in pituitary tumorigenesis.

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RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling

Cancer Research ◽

10.1158/0008-5472.can-18-2796 ◽

2019 ◽

Vol 80 (2) ◽

pp. 219-233 ◽

Cited By ~ 4

Author(s):

Xin-Yi Loh ◽

Qiao-Yang Sun ◽

Ling-Wen Ding ◽

Anand Mayakonda ◽

Nachiyappan Venkatachalam ◽

...

Keyword(s):

Cell Cycle ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Cell Cycle Signaling

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G1 Transcription Factors Are Differentially Regulated in Saccharomyces cerevisiae by the Swi6-Binding Protein Stb1

Molecular and Cellular Biology ◽

10.1128/mcb.23.14.5064-5077.2003 ◽

2003 ◽

Vol 23 (14) ◽

pp. 5064-5077 ◽

Cited By ~ 45

Author(s):

Michael Costanzo ◽

Oliver Schub ◽

Brenda Andrews

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Transcription Factors ◽

Transcriptional Activation ◽

Chromatin Immunoprecipitation ◽

Cell Cycle Regulation ◽

Binding Protein ◽

Microarray Studies ◽

Cycle Regulation ◽

Integral Feature

ABSTRACT Stage-specific transcriptional programs are an integral feature of cell cycle regulation. In the budding yeast Saccharomyces cerevisiae, over 120 genes are coordinately induced in late G1 phase by two heterodimeric transcription factors called SBF and MBF. Activation of SBF and MBF is an upstream initiator of key cell cycle events, including budding and DNA replication. SBF and MBF regulation is complex and genetically redundant, and the precise mechanism of G1 transcriptional activation is unclear. Assays using SBF- and MBF-specific reporter genes revealed that the STB1 gene specifically affected MBF-dependent transcription. STB1 encodes a known Swi6-binding protein, but an MBF-specific function had not been previously suspected. Consistent with a specific role in regulating MBF, a STB1 deletion strain requires SBF for viability and microarray studies show a decrease in MBF-regulated transcripts in a swi4Δ mutant following depletion of Stb1. Chromatin immunoprecipitation experiments confirm that Stb1 localizes to promoters of MBF-regulated genes. Our data indicate that, contrary to previous models, MBF and SBF have unique components and might be distinctly regulated.

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