Tumor suppressor
            <scp>PNRC</scp>
            1 blocks r
            <scp>RNA</scp>
            maturation by recruiting the decapping complex to the nucleolus

Gaviraghi, Marco; Vivori, Claudia; Sanchez, Yerma Pareja; Invernizzi, Francesca; Cattaneo, Angela; Santoliquido, Benedetta Maria; Frenquelli, Michela; Segalla, Simona; Bachi, Ángela; Doglioni, Claudio; Pelechano, Vicent; Cittaro, Davide; Tonon, Giovanni

doi:10.15252/embj.201899179

Cited by 36 publications

(37 citation statements)

References 83 publications

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“…The length of the U8-DII snoRNAs is quite similar to most C/D box snoRNAs (Table 1 and Supplemental Figures SF1 and SF3). U3-DII and U8-DII snoRNAs are reported before (13,41) and are likely a result of the removal of the mono-methylated (m 7 G) 5’ cap by the decapping complex, which is regulated by PNRC1 (42) although we cannot completely rule out that they also could originate from an alternative transcriptional start site (Figure 1A).…”

Section: Resultsmentioning

confidence: 60%

Maternal- and somatic-type snoRNA expression and processing in zebrafish development

Pagano¹,

Locati²,

Ensink³

et al. 2019

Preprint

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Maternal-and somatic-type snoRNAs in zebrafishU3 U8 snoRNA, maternal expression, RNA processing, embryogenesis 1 ABSTRACT 2 Small nucleolar RNAs (snoRNAs) are non-coding RNAs that play an important role in the 3 complex maturation process of ribosomal RNAs (rRNAs). SnoRNAs are categorized in classes, 4 with each class member having several variants present in a genome. Similar to our finding 5 of specific rRNA expression types in zebrafish embryogenesis, we discovered preferential 6 maternal-and somatic-expression for snoRNAs. Most snoRNAs and their variants have 7 higher expression levels in somatic tissues than in eggs, yet we identified three snoRNAs; 8 U3, U8 and snoZ30 of which specific variants show maternal-or somatic-type expression.9 For U3 and U8 we also found small-derived snoRNAs that lack their 5' rRNA recognition part 10 and are essentially Domain II hairpin structures (U-DII). These U-DII snoRNAs from variants 11 showed similar preferential expression, in which maternal-type variants are prominently 12 expressed in eggs and subsequently replaced by a somatic-type variants during 13 embryogenesis. This differential expression is related to the organization in tandem repeats 14 (maternal type) or solitary (somatic-type) genes of the involved U snoRNA loci. The 15 collective data showed convincingly that the preferential expression of snoRNAs is achieved 16 by transcription regulation, as well as through RNA processing. Finally, we observed small-17 RNAs derived from internal transcribed spacers (ITSs) of a U3 snoRNA loci that via 18 complementarity binding, may be involved in the biosynthesis of U3-DII snoRNAs.19 Altogether, the here described maternal-and somatic-type snoRNAs are the latest addition 20 to the developing story about the dual ribosome system in zebrafish development. 22 INTRODUCTION23 Small nucleolar RNAs (snoRNAs) are a class of non-coding RNA molecules of variable length 24 (the majority being 60-200 nucleotides long), found in archaea and eukaryotes (1). SnoRNAs 3 25 are thought to mainly be involved in post-transcriptional modifications and maturation of 26 ribosomal RNAs (rRNAs) (2,3). However, recently additional functions have been ascribed to 27 specific snoRNAs, from regulation of mRNA editing and splicing (4) to post-transcriptional 28 gene silencing (5,6). SnoRNAs do not possess any intrinsic catalytic or modification activity, 29 but act both as a scaffold for partner proteins, forming small nucleolar ribonucleoproteins 30 (snoRNPs) and as guide for target specificity (7). Based on base-pairing interactions with 31 their target RNA, snoRNAs can thus direct the associated catalytic protein subunits to 32 accurately modify a specific RNA site (8).33 In general, eukaryotic genomes can contain up to 200+ unique snoRNA genes (9). Based on 34 the presence of conserved sequence motifs, the majority of snoRNAs are classified into two 35 distinct classes: box C/D snoRNAs, which guide 2'-O-methylation of ribose, and box H/ACA 36 snoRNAs, which are involved in the isomerization of sp...

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Section: Resultsmentioning

confidence: 60%

Maternal- and somatic-type snoRNA expression and processing in zebrafish development

Pagano¹,

Locati²,

Ensink³

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Because of the decapping enzymes which has the enzyme activity to remove the cap structure from the 5′ end of mRNA transcripts [44, 45], decapping enzymes has been reported closely related to the development in multiple diseases. For example, decapping enzyme Nudt3, a member of nudix hydrolase superfamily, promoting MCF7 cell migration and proliferation by modulating β6 and lipocalin-2 mRNA stability [46]; Dcp2, the first discovered decapping enzyme, enhanced tumor cell growth by affected RAS and MYC mRNA stability [47].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of NPL4 promotes bladder cancer cell proliferation by inhibiting DXO destabilization of cyclin D1 mRNA

Lu¹,

Yin²,

Zhang³

et al. 2019

Cancer Cell Int

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Background NPL4 is an important cofactor of the valosin-containing protein (VCP)–NPL4–UFD1 complex. The VCP–NPL4–UFD1 has been considered as a ubiquitin proteasome system (UPS) regulator and response to protein degradation. While NPL4 plays important roles in various diseases, little is known about its functions in bladder cancer (BC). Methods MTT assays and colony forming test were performed to evaluate cell proliferation ability and Western blotting was used to detect protein expression. Cyclin D1 mRNA expression was detected using qRT-PCR, and coimmunoprecipitation (CoIP) was used to detect protein–protein interactions. Results NPL4 was upregulated in BC tissue and correlated with poor prognosis. Upregulation of NPL4 promoted cell proliferation while suppression of NPL4 reduced BC cell proliferation. Upregulation of NPL4 led to overexpression of cyclin D1 by enhancing its mRNA stability. Moreover, NPL4 was found to bind directly to DXO and induce its degradation. DXO was downregulated in BC tissue and regulated BC cell proliferation by destabilizing cyclin D1 mRNA. DXO-mediated NPL4 regulated BC cell proliferation by stabilizing cyclin D1 expression. Conclusions The NPL4/DXO/cyclin D1 axis exert crucial role in BC cell growth and is associated with prognosis and may represent a potential therapeutic target for BC.

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“…[38,39] By decapping a subset of mRNAs, DCP2 plays an important role in cancer pathogenesis by affecting processes such as cell migration and apoptosis. [40][41][42][43][44] More interestingly, DCP2 is regulated at the post-transcriptional level rather than being transcriptionally silenced, and miRNAs are an effective way to down-regulate DCP2. DCP2 mRNA has a fairly long 3′-UTR of 7.2 kb that may contain many potential miRNA binding sites.…”

Section: Discussionmentioning

confidence: 99%

miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation

Zhang

Yan

et al. 2020

Preprint

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Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.

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Tumor suppressor PNRC 1 blocks r RNA maturation by recruiting the decapping complex to the nucleolus

Cited by 36 publications

References 83 publications

Maternal- and somatic-type snoRNA expression and processing in zebrafish development

Maternal- and somatic-type snoRNA expression and processing in zebrafish development

Upregulation of NPL4 promotes bladder cancer cell proliferation by inhibiting DXO destabilization of cyclin D1 mRNA

miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation

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