IMP-3 protects the mRNAs of cyclins D1 and D3 from GW182/AGO2-dependent translational repression

Deforzh, Evgeny; Vargas, Thaiz Rivera; Kropp, Jeremie; Vandamme, Marie; Pinna, Guillaume; Polesskaya, Anna

doi:10.3892/ijo.2016.3750

Cited by 11 publications

(13 citation statements)

References 24 publications

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“…While investigating the role of DDX5 in cell cycle regulation in spermatogonia, we identified and confirmed interaction of DDX5 with ILF3 and its protein partners ILF2 and IGF2BP3 57,58 (Fig. 4b and Supplementary Data 3).…”

Section: Resultsmentioning

confidence: 54%

“…6b). Previous studies have demonstrated that ILF3 is involved in post-transcriptional regulation of cyclin mRNAs 57,62 . Therefore, we performed ILF3 RIP-qPCR experiments in cultured wildtype spermatogonia to identify cyclin mRNAs bound to ILF3 and elucidate a potential co-regulatory role with DDX5.…”

Section: Resultsmentioning

confidence: 99%

“…ILF3 regulates the stability of Ccne1 mRNA by direct binding to its 3’-UTR and post-transcriptionally regulates Ccnd1 through interactions with IGF2BP3 57,62 . Given the DDX5/ILF3 interaction and known role of ILF3 in cyclin transcript regulation, we sought to determine whether loss of Ilf3 in undifferentiated spermatogonia would result in a phenotype similar to that observed upon loss of Ddx5 .…”

Section: Resultsmentioning

confidence: 99%

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DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

et al. 2019

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Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia.

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Section: Resultsmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

et al. 2019

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“…In addition, IMP3 is a crucial transcriptional regulator, which binds a couple of mRNAs and modulates their expressions 20–22. IMP-3 binds to and positively regulates the expressions of cyclins D1, D3 and G1 in a number of human cancer cell lines 20,21. IMP3 also binds avidly to SNAI2 mRNA and regulates its expression by binding to the 5‘ UTR 22.…”

Section: Discussionmentioning

confidence: 99%

<p>Insulin-like growth factor II mRNA-binding protein 3 promotes cell proliferation, migration and invasion in human glioblastoma</p>

Wu¹,

Ma²,

Qi³

et al. 2019

OTT

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Background/Aims: Recently, the insulin-like growth factor mRNA-binding protein 3 (IMP3) has been reported to be involved in tumorigenesis. We aimed to study the expression and role of IMP3 in human glioblastoma. Methods: We analyzed the expression of IMP3 in 70 cases of glioma tissues, normal brain tissues and 5 kinds of cell lines using western blot. Immunohistochemistry (IHC) was used to evaluate the expression and distribution of IMP3 in glioma tissues. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of IMP3 in vitro and in vivo. The epithelial-mesenchymal transition (EMT)-related biomarkers were detected by western blot. Results: We found that the expression level of IMP3 was obviously higher in glioma tissues than that in normal brain tissues, and associated with glioma grade. In-vitro assays revealed that IMP3 overexpression significantly induced cell proliferation, migration, and invasion. Mechanically, IMP3 over-expression downregulated the expression of E-cadherin, but upregulated the expressions of N-cadherin, vimentin, snail, slug and MMP9. However, the inhibition of IMP3 impaired these oncogenic effects. In vivo assay also demonstrated that silencing of IMP3 inhibited tumor growth and improved survival of tumor-bearing xenograft nude mice. Conclusion: IMP3 can promote cell proliferation, migration and invasion by inducing EMT in glioblastoma. Thus, targeting IMP3 pathway may be a novel way to treat patients with glioblastoma.

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“…At the same time, analysis of LINC01420 RNA-binding proteins revealed that many of them are involved in regulation of mRNA nuclear export, translation and stability (e.g. EIF4A3 [44], IGF2BP1 [45], IGF2BP2 [46], IGF2BP3 [47], UPF1 [48]). It indicates the protein coding function of this transcript.…”

Section: Discussionmentioning

confidence: 99%

LINC01420 RNA structure and influence on cell physiology

2019

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Background: It was shown that the major part of human genome is transcribed and produces a large number of long noncoding RNAs (lncRNAs). Today there are many evidences that lncRNAs play important role in the regulation of gene expression during different cellular processes. Moreover, lncRNAs are involved in the development of various human diseases. However, the function of the major part of annotated transcripts is currently unknown, whereas different lncRNAs annotations tend to have low overlap. Recent studies revealed that some lncRNAs have small open reading frames (smORFs), that produce the functional microproteins. However, the question whether the function of such genes is determined by microprotein or RNA itself or both remains open. Thus, the study of new lncRNA genes is important to understanding the functional role of such a heterogeneous class of genes.Results: In the present study, we used reverse transcription PCR and rapid amplification of cDNA ends (RACE) analysis to determine the structure of the LINC01420 transcript. We revealed that LINC01420 has two isoforms that differ in length of the last exon and are localized predominantly in the cytoplasm. We showed that expression of the short isoform is much higher than the long. Besides, MTT and wound-healing assays revealed that LINC01420 inhibited cell migration in human melanoma cell line A375, but does not influence on cell viability. Conclusion: During our work, D'Lima et al. found smORF in the first exon of the LINC01420 gene. This smORF produces functional microprotein named non-annotated P-body dissociating polypeptide (NoBody). However, our results provide new facts about LINC01420 transcript and its function.

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IMP-3 protects the mRNAs of cyclins D1 and D3 from GW182/AGO2-dependent translational repression

Cited by 11 publications

References 24 publications

DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

<p>Insulin-like growth factor II mRNA-binding protein 3 promotes cell proliferation, migration and invasion in human glioblastoma</p>

LINC01420 RNA structure and influence on cell physiology

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