The RNA-binding protein Sam68 regulates tumor cell viability and hepatic carcinogenesis by inhibiting the transcriptional activity of FOXOs

AbstractRBM10 is an RNA-binding protein that regulates alternative splicing (AS). This protein localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs). We investigated the biological significance of RBM10 localization to S1-1 NBs, which is poorly understood. Our analyses revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs acted synergistically and were sufficient for localization of RBM10 to S1-1 NBs. Furthermore, the C2H2 ZnF not only acted as an NBTS, but was also essential for regulation of AS by RBM10. RBM10 did not participate in S1-1 NB formation. We confirmed the previous finding that localization of RBM10 to S1-1 NBs increases as cellular transcriptional activity decreases and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in these structures via its NBTSs when cellular transcription decreases. We propose that the NB-targeting activity of the C2H2 ZnF is induced when it is not bound to pre-mRNA or the splicing machinery complex under conditions of reduced transcription.

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Faculty Opinions recommendation of ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.740857859.793590646 ◽

2021 ◽

Author(s):

Ferdinando Auricchio

Keyword(s):

Drug Resistance ◽

Tumor Cell ◽

Cell Survival ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Tumor Cell Survival

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Stimulation of Ki-ras Ribozyme Activity by RNA Binding Protein, NCp7, in Vitro and in Pancreatic Tumor Cell Line, Capan 1

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1994.tb17261.x ◽

1994 ◽

Vol 733 (1 Molecular and) ◽

pp. 113-121 ◽

Cited By ~ 3

Author(s):

KARIN MOELLING ◽

GERD MUELLER ◽

JENS DANNULL ◽

CHRISTOPH REUSS ◽

PETER BEIMLING ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Pancreatic Tumor ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Tumor Cell Line ◽

Pancreatic Tumor Cell ◽

Stimulation Of

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A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000494155 ◽

2018 ◽

Vol 50 (2) ◽

pp. 437-451 ◽

Cited By ~ 8

Author(s):

Le Bao ◽

Lei Yuan ◽

Pengfei Li ◽

Qingyun Bu ◽

Aijun Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Cell Viability ◽

Rna Binding ◽

Binding Protein ◽

Hippo Pathway ◽

Rna Binding Protein ◽

Luciferase Reporter ◽

Western Blots ◽

Qrt Pcr

Background/Aims: The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions. Finally, qRT-PCR and western blot analysis were used to detect the levels of FUS and LATS1/2 in HCC and adjacent normal tissues, and the correlation between them in HCC tissues. Results: Overexpression of FUS decreased cell viability, migration, invasion and stemness. Moreover, FUS interacted and stabilized LATS1/2 stability, and thus promoted LATS1/2 expression and activated Hippo pathway. Finally, FUS and LAST1/2 levels were positively correlated and significantly down-regulated in HCC tissues. Conclusion: We demonstrate that FUS/LATS1/2 axis inhibits HCC progression via activating Hippo pathway.

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Erwinia carotovora Subspecies Produce Duplicate Variants of ExpR, LuxR Homologs That Activate rsmA Transcription but Differ in Their Interactions with N-Acylhomoserine Lactone Signals

Journal of Bacteriology ◽

10.1128/jb.00351-06 ◽

2006 ◽

Vol 188 (13) ◽

pp. 4715-4726 ◽

Cited By ~ 46

Author(s):

Yaya Cui ◽

Asita Chatterjee ◽

Hiroaki Hasegawa ◽

Arun K. Chatterjee

Keyword(s):

Transcriptional Activity ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Erwinia Carotovora ◽

Negative Regulator ◽

Signaling System ◽

Gene Encoding ◽

Acylhomoserine Lactone ◽

Luxr Homolog

ABSTRACT The N-acylhomoserine lactone (AHL) signaling system comprises a producing system that includes acylhomoserine synthase (AhlI, a LuxI homolog) and a receptor, generally a LuxR homolog. AHL controls exoprotein production in Erwinia carotovora and consequently the virulence for plants. In previous studies we showed that ExpR, a LuxR homolog, is an AHL receptor and that it activates transcription of rsmA, the gene encoding an RNA binding protein which is a global negative regulator of exoproteins and secondary metabolites. An unusual finding was that the transcriptional activity of ExpR was neutralized by AHL. We subsequently determined that the genomes of most strains of E. carotovora subspecies tested possess two copies of the expR gene: expR1, which was previously studied, and expR2, which was the focus of this study. Comparative analysis of the two ExpR variants of E. carotovora subsp. carotovora showed that while both variants activated rsmA transcription, there were significant differences in the patterns of their AHL interactions, the rsmA sequences to which they bound, and their relative efficiencies of activation of rsmA transcription. An ExpR2− mutant produced high levels of exoproteins and reduced levels of RsmA in the absence of AHL. This contrasts with the almost complete inhibition of exoprotein production and the high levels of RsmA production in an AhlI− mutant that was ExpR1−. Our results suggest that ExpR2 activity is responsible for regulating exoprotein production primarily by modulating the levels of an RNA binding protein.

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