Ribosomal protein pNO40 mediates nucleolar sequestration of SR family splicing factors and its overexpression impairs mRNA metabolism

Lin, Yen-Ming; Chu, Pao‐Hsien; Li, Yun-Zhu; Ouyang, Pin

doi:10.1016/j.cellsig.2017.01.010

Cited by 10 publications

(14 citation statements)

References 22 publications

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“…S5). As expected from our human immunohistochemistry and prior literature (Chang et al, 2003;Lin et al, 2017;Ouyang, 2009), ZCCHC17 is localized primarily to the nucleus of rat cortical neuronal cultures. Introducing ZCCHC17 siRNA led to a reduction of approximately 50% of ZCCHC17 protein.…”

Section: Zcchc17 Loss Correlates With Loss Of Synaptic Genes In Adsupporting

confidence: 87%

“…ZCCHC17 is a poorly understood protein that has been shown to interact with transcription factors (Chang et al, 2003;Joo et al, 2010) as well as splicing factors (Lin et al, 2017;Ouyang, 2009). ZCCHC17 contains a zinc-finger (CCHC) domain and a nuclear localization signal, and microscopy has localized ZCCHC17 to the nucleus and nucleolus (Chang et al, 2003;Gueydan et al, 2002;Lin et al, 2017;Ouyang, 2009). Although there is no published experimental study of ZCCHC17 protein in brain tissue, a recent metaanalysis of RNA expression data from six previous gene expression studies of AD brain tissue included ZCCHC17 as one of the top 30 most reliably downregulated genes in AD (Li et al, 2015).…”

Section: Zcchc17 Loss Correlates With Loss Of Synaptic Genes In Admentioning

confidence: 99%

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ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer’s disease

Tomljanovic¹,

Patel

Shin

et al. 2017

Bioinformatics

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Section: Zcchc17 Loss Correlates With Loss Of Synaptic Genes In Adsupporting

confidence: 87%

Section: Zcchc17 Loss Correlates With Loss Of Synaptic Genes In Admentioning

confidence: 99%

ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer’s disease

Tomljanovic¹,

Patel

Shin

et al. 2017

Bioinformatics

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“…Formation of these proteasome-foci might probably affect 26S proteasome assembly or potential modifications required for optimal proteasome activity. The nucleolus is involved in the confinement of nuclear proteins through interactions with long non-coding RNAs (Audas et al, 2012a ) or with the ribosomal protein pNON40 (Lin et al, 2017 ). Thus, it is reasonable to consider that nucleolus might be involved in the regulation of proteasome assembly or activity through a RNA or protein dependent nucleolar sequestering mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…An important property of the nucleolus is that it sequesters a large number of nuclear genes from which RNA polymerases II and III are normally excluded and hence it might play a key role in regulating gene expression (Németh et al, 2010 ; Németh and Längst, 2011 ; Padeken and Heun, 2014 ; Pontvianne et al, 2016b ). The nucleolus has also novel and poorly characterized functions in protein sequestering via interaction with other proteins and/or long non-coding RNAs (Audas et al, 2012a , b ; Jacob et al, 2012 ; Lin et al, 2017 ). The nucleolar retention of specific proteins can potentially suppress or inhibit diverse cellular activities by recruiting general transcription or RNA processing factors or other proteins involved in protein dynamic and activities.…”

Section: Introductionmentioning

confidence: 99%

Nucleolar Proteome Analysis and Proteasomal Activity Assays Reveal a Link between Nucleolus and 26S Proteasome in A. thaliana

et al. 2017

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In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity.

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“…SRSF2 is a 35 kDa serine/arginine-rich protein, which belongs to the highly conserved splicing factor family in higher eukaryotes, contributing to gene splicing and alternative splicing. SRSF2 plays a key role in additional interactions between the various steps in expression of the SRSF2 gene, and can also regulate transcriptional activation and elongation [21]. By interacting with transcription factor E2F1, SRSF2 stimulation regulates cell cycle gene activity [22].…”

Section: Introductionmentioning

confidence: 99%

miR-193a-3p Promotes Radio-Resistance of Nasopharyngeal Cancer Cells by Targeting SRSF2 Gene and Hypoxia Signaling Pathway

Kong

Wei

et al. 2019

Med Sci Monit Basic Res

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Background Radio-resistance is an important barrier in nasopharyngeal carcinoma treatment. MicroRNAs are gene expression core regulators in various biological procedures containing cancer radio-resistance. Nevertheless, the clinical association between nasopharyngeal carcinoma and miR-193a-3p/SRSF2 remains unclear. Material/Methods We examined the miR-193a-3p level in radio-sensitive CNE-2 and radio-resistant CNE-1 NPC cell lines, and, based on a literature review, predicted SRSF2 to be the target gene of miR-193a-3p. We explored the expression of SRSF2 at protein and mRNA levels by transfecting either miR-193a-3p-mimic or antagomiR. Finally, we performed signaling pathway analysis to assess the possible role of miR-193a-3p/SRSF2 in signaling pathways. Results miR-193a-3p promotes NPC radio-resistance, and the SRSF2 gene is the direct target for miR-193a-3p in NPC, and thus is negatively correlated with NPC radio-resistance. The hypoxia signaling pathway activity is strongly affected, and it is possible to use the downstream activity of the SRSF2 gene to show the effect of miR-193a-3p on radio-resistance in NPC cells. Conclusions miR-193a-3p mediates promotion of NPC radio-resistance.

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Ribosomal protein pNO40 mediates nucleolar sequestration of SR family splicing factors and its overexpression impairs mRNA metabolism

Cited by 10 publications

References 22 publications

ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer’s disease

ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer’s disease

Nucleolar Proteome Analysis and Proteasomal Activity Assays Reveal a Link between Nucleolus and 26S Proteasome in A. thaliana

miR-193a-3p Promotes Radio-Resistance of Nasopharyngeal Cancer Cells by Targeting SRSF2 Gene and Hypoxia Signaling Pathway

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