Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes

Eto, Kojiro; Sonoda, Yoshiyuki; Jin, Yuji; Abe, Shinichi

doi:10.1016/j.bbrc.2010.02.014

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Since NIPP1 controls the dephosphorylation of FHA ligands by associated PP1 (see Introduction), we hypothesize that the proliferation defect in NIPP1-depleted testis stems from an altered phosphorylation status of FHA ligands. Among the established NIPP1 FHA ligands, the histone methyltransferase EZH1/2 and the splicing factor SAP155 are good candidates to mediate the testicular phenotype in the iKOs because these proteins have established functions in spermatogenesis 52 – 54 . However, we cannot exclude that other, hitherto unknown FHA ligands, contribute to the testicular phenotype.…”

Section: Discussionmentioning

confidence: 99%

The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis

Ferreira

Boens

Winkler

et al. 2017

Sci Rep

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NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. The inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very efficiently in testis and resulted in a gradual loss of germ cells, culminating in a Sertoli-cell only phenotype. Before the overt development of this phenotype Ppp1r8 −/− testis showed a decreased proliferation and survival capacity of cells of the spermatogenic lineage. A reduced proliferation was also detected after the tamoxifen-induced removal of NIPP1 from cultured testis slices and isolated germ cells enriched for undifferentiated spermatogonia, hinting at a testis-intrinsic defect. Consistent with the observed phenotype, RNA sequencing identified changes in the transcript levels of cell-cycle and apoptosis regulating genes in NIPP1-depleted testis. We conclude that NIPP1 is essential for mammalian spermatogenesis because it is indispensable for the proliferation and survival of progenitor germ cells, including (un)differentiated spermatogonia.

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Section: Discussionmentioning

confidence: 99%

The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis

Ferreira

Boens

Winkler

et al. 2017

Sci Rep

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show abstract

“…Recent studies have suggested that lncRNAs could regulate alternative splicing (Wang et al 1998 ; Eto et al 2010 ; Misteli et al 1997 ). The main mechanisms can be categorized into three types: (i) lncRNAs interact with specific splicing factors, (ii) lncRNAs bind to pre-mRNA molecules, and (iii) lncRNAs affect chromatin remodeling.…”

Section: Discussionmentioning

confidence: 99%

The long non-coding RNA DKFZp434J0226 regulates the alternative splicing process through phosphorylation of SF3B6 in PDAC

Tong

et al. 2021

Mol Med

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Background Long noncoding RNAs (lncRNAs), a type of pervasive genes that regulates various biological processes, are differentially expressed in different types of malignant tumors. The role of lncRNAs in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we investigated the role of the lncRNA DKFZp434J0226 in PDAC. Methods Aberrantly expressed mRNAs and lncRNAs among six PDAC and paired non-tumorous tissues were profiled using microarray analysis. Quantitative real-time polymerase chain reaction was used to evaluate DKFZp434J0226 expression in PDAC tissues. CCK-8 assay, wound-healing assay, soft agar colony formation assay, and transwell assay were performed to assess the invasiveness and proliferation of PDAC cells. Furthermore, RNA pull-down, immunofluorescence, RNA immunoprecipitation, and western blotting assays were performed to investigate the association between DKFZp434J0226 and SF3B6. Tumor xenografts in mice were used to test for tumor formation in vivo. Results In our study, 222 mRNAs and 128 lncRNAs were aberrantly expressed (≥ twofold change). Of these, 66 mRNAs and 53 lncRNAs were upregulated, while 75 lncRNAs and 156 mRNAs were downregulated. KEGG pathway analysis and the Gene ontology category indicated that these genes were associated with the regulation of mRNA alternative splicing and metabolic balance. Clinical analyses revealed that overexpression of DKFZp434J0226 was associated with worse tumor grading, frequent perineural invasion, advanced tumor-node-metastasis stage, and decreased overall survival and time to progression. Functional assays demonstrated that DKFZp434J0226 promoted PDAC cell migration, invasion, and growth in vitro and accelerated tumor proliferation in vivo. Mechanistically, DKFZp434J0226 interacted with the splicing factor SF3B6 and promoted its phosphorylation, which further regulated the alternative splicing of pre-mRNA. Conclusions This study indicates that DKFZp434J0226 regulates alternative splicing through phosphorylation of SF3B6 in PDAC and leads to an oncogenic phenotype in PDAC.

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“…The spliceosome is a type of macromolecular complex that regulates RNA-RNA binding and mediates the processing of precursor mRNA into mRNA. SAP155, an essential component of the spliceosome, is expressed in the mouse testes (Eto et al 2010). Major spliceosome defects affect testicular spermatogonia differentiation and inhibit sperm development and maturation; these issues are linked with the development of nonobstructive azoospermia (Wu et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Comparison of proteomic profiles from the testicular tissue of males with impaired and normal spermatogenesis

Liang

Zheng

Zeng

et al. 2020

Systems Biology in Reproductive Medicine

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Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes

Cited by 9 publications

References 28 publications

The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis

The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis

The long non-coding RNA DKFZp434J0226 regulates the alternative splicing process through phosphorylation of SF3B6 in PDAC

Comparison of proteomic profiles from the testicular tissue of males with impaired and normal spermatogenesis

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