CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing

Advanced Science, Год журнала: 2024, Номер 11(31)

Опубликована: Июнь 18, 2024

The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation pre-mRNA alternative splicing (AS) at post-transcriptional level. However, fundamental mechanism AS in remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting sterility, impaired characterized by increased apoptosis decreased differentiated spermatogonia spermatocytes observed. That interacted with several spliceosome proteins participate proper assembly stability discovered. By integrating RNA-seq LACE-seq data, further confirmed directly bound regulated genes related (Znhit1, Btrc, Fbxw7) RNA (Rbfox1, Celf1, Rbm10). Additionally, can indirectly amplify its effect through modulating RBFOX1. Collectively, this research establishes orchestrates factor network ensure accurate during early steps spermatogenesis.

Язык: Английский

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Wnt/β-catenin pathway in arrhythmogenic cardiomyopathy

Oncotarget, Год журнала: 2017, Номер 8(36), С. 60640 - 60655

Опубликована: Апрель 27, 2017

// Alessandra Lorenzon 1 , Martina Calore 2 Giulia Poloni Leon J. De Windt Paola Braghetta 3 and Rampazzo University of Padua, Department Biology, Italy Maastricht University, Cardiology, Maastricht, The Netherlands Molecular Medicine, Correspondence to: Rampazzo, email: [email protected] Keywords: Wnt, β-catenin, microRNAs, arrhythmogenic cardiomyopathy, molecular pathogenesis Received: January 30, 2017 Accepted: April 14, Published: 27, ABSTRACT Wnt/β-catenin signaling pathway plays essential roles in heart development as well cardiac tissue homoeostasis adults. Abnormal regulation this is linked to a variety disease conditions, including hypertrophy, fibrosis, arrhythmias, infarction. Recent studies on genetically modified cellular animal models document crucial role the cardiomyopathy (AC), an inherited intercalated discs, typically characterized by ventricular arrhythmias progressive substitution myocardium with fibrofatty tissue. In review, we summarize conflicting published data regarding contribution AC report identification new potential therapeutic molecule that prevents myocyte injury dysfunction due desmosome mutations vitro vivo interfering pathway. Finally, underline function epigenetic regulatory RNA factors reported participate several pathological responses Wnt network, important modulators transduction AC. Elucidation precise mechanism could provide fundamental insights for mechanism-based strategy delay onset or progression disease.

Язык: Английский

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The RNA-binding landscape of RBM10 and its role in alternative splicing regulation in models of mouse early development

RNA Biology, Год журнала: 2016, Номер 14(1), С. 45 - 57

Опубликована: Окт. 20, 2016

Mutations in the RNA-binding protein, RBM10, result a human syndromic form of cleft palate, termed TARP syndrome. A role for RBM10 alternative splicing regulation has been previously demonstrated cell lines. To uncover cellular functions line that is relevant to phenotype observed syndrome, we used iCLIP identify its endogenous RNA targets mouse embryonic mandibular line. We binds pre-mRNAs with significant enrichment intronic regions, agreement this protein pre-mRNA splicing. In addition protein-coding transcripts, also variety RNAs, including non-coding such as spliceosomal small nuclear U2 and U12. RNA-seq was investigate changes gene expression KO cells ES cells. uncovered common transcripts both lines but identified cell-type specific events. Importantly, those display contain tags, suggesting direct these Finally, show depletion leads proliferation defects gross alterations their differentiation potential. These results demonstrate two models early development suggests mutations could lead affect normal palate cause disease.

Язык: Английский

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A positive feedback loop of lncRNA-RMRP/ZNRF3 axis and Wnt/β-catenin signaling regulates the progression and temozolomide resistance in glioma

Cell Death and Disease, Год журнала: 2021, Номер 12(11)

Опубликована: Окт. 16, 2021

Abstract Drug resistance strikingly limits the therapeutic effect of temozolomide (TMZ) (a common drug for glioma). Long non-coding RNA (lncRNA) RMRP has been found to be implicated in glioma progression. However, on TMZ along with related molecular mechanisms is poorly defined glioma. In present study, RMRP, ZNRF3, and IGF2BP3 were screened out by bioinformatics analysis. The expression levels lncRNAs mRNAs measured RT-qPCR assay. Protein genes detected western blot immunofluorescence assays. ZNRF3 mRNA stability was analyzed using Actinomycin D Cell proliferative ability survival rate determined CCK-8 apoptotic pattern estimated flow cytometry. knockdown growth TMZ-treated xenograft tumors explored vivo. relationships IGF2BP3, prediction analysis, immunoprecipitation, luciferase, pull-down, chromatin immunoprecipitation results showed that highly expressed curbed cell proliferation, facilitated apoptosis reduced cells, hindered tumors. exerted its functions down-regulating cells. interacted mRNA. weakened interaction Argonaute 2 (Ago2) ZNRF3. IGF2BP3. inhibited β-catenin up-regulating inhibition Wnt/β-catenin signaling pathway XAV-939 RMRP-mediated promoted TCF4 conclusion, RMRP/ZNRF3 axis formed a positive feedback loop regulate sustained activation might contribute better management cancers.

Язык: Английский

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Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications

Cellular Oncology, Год журнала: 2021, Номер 44(3), С. 473 - 494

Опубликована: Март 11, 2021

Язык: Английский

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