更新于：2024-09-19

MOV10L1

更新于：2024-09-19

基本信息

别名

CHAMP、DJ402G11.8、DKFZp434B0717

+ [5]

简介

ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the primary piRNA metabolic process. Specifically binds to piRNA precursors and promotes the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Acts via its ATP-dependent RNA helicase activity: displays 5'-3' RNA unwinding activity and probably mediates unwinding and funneling of single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins.

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100 项与 MOV10L1 相关的临床结果

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100 项与 MOV10L1 相关的转化医学

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0 项与 MOV10L1 相关的专利（医药）

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项与 MOV10L1 相关的文献（医药）

2023-05-01·PLoS genetics

The MOV10 RNA helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice

Article

作者: Mourelatos, Zissimos ; Guan, Yongjuan ; Maragkakis, Manolis ; Wang, P Jeremy ; Liang, Guanxiang ; Kang, Zhenlong ; Vourekas, Anastassios ; Gao, Hongyan ; Leu, N Adrian ; Alexiou, Panagiotis

Transposable elements constitute nearly half of the mammalian genome and play important roles in genome evolution.While a multitude of both transcriptional and post-transcriptional mechanisms exist to silence transposable elements, control of transposition in vivo remains poorly understood.MOV10, an RNA helicase, is an inhibitor of mobilization of retrotransposons and retroviruses in cell culture assays.Here we report that MOV10 restricts LINE1 retrotransposition in mice.Although MOV10 is broadly expressed, its loss causes only incomplete penetrance of embryonic lethality, and the surviving MOV10-deficient mice are healthy and fertile.Biochem., MOV10 forms a complex with UPF1, a key component of the nonsense-mediated mRNA decay pathway, and primarily binds to the 3' UTR of somatically expressed transcripts in testis.Consequently, loss of MOV10 results in an altered transcriptome in testis.Analyses using a LINE1 reporter transgene reveal that loss of MOV10 leads to increased LINE1 retrotransposition in somatic and reproductive tissues from both embryos and adult mice.Moreover, the degree of LINE1 retrotransposition inhibition is dependent on the Mov10 gene dosage.Furthermore, MOV10 deficiency reduces reproductive fitness over successive generations.Our findings demonstrate that MOV10 attenuates LINE1 retrotransposition in a dosage-dependent manner in mice.

2022-05-30·Human Reproduction1区 · 医学

Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes

1区 · 医学

Article

作者: Jaillard, S ; Swierkowski-Blanchard, N ; Albert, M ; Dieudonne, M N ; Mandon-Pepin, B ; Prasivoravong, J ; Hue, C ; Mambu Mambueni, H ; Ghieh, F ; Molina-Gomes, D ; Garchon, H J ; Delcroix, M ; Vialard, F ; Bailly, M ; Fortemps, J ; Serazin, V ; Gerault, C ; Marcelli, F ; Izard, V ; Leroy, C ; Barbotin, A L ; Louboutin, A ; Ferlicot, S

AbstractSTUDY QUESTIONCould whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)?SUMMARY ANSWERWES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA.WHAT IS KNOWN ALREADYAt present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE.STUDY DESIGN, SIZE, DURATIONIn a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE.PARTICIPANTS/MATERIALS, SETTING, METHODSTwenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein.MAIN RESULTS AND THE ROLE OF CHANCEDeleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)].LARGE SCALE DATAData available on requestLIMITATIONS, REASONS FOR CAUTIONMore data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings.WIDER IMPLICATIONS OF THE FINDINGSOur results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene—confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

2021-10-01·Arthritis & Rheumatology1区 · 医学

Pim Kinases as Therapeutic Targets in Early Rheumatoid Arthritis

1区 · 医学

Article

作者: Herron, Ian ; Isaacs, John D. ; Mellor, Andrew L. ; Maney, Nicola J. ; Pratt, Arthur G. ; Barron‐Millar, Ben ; Lemos, Henrique ; Carey, Christopher ; Anderson, Amy E.

ObjectiveAs well as being an established oncoprotein and therapeutic target in cancer, proviral integration site for Moloney murine leukemia virus 1 (Pim‐1) is implicated in human autoimmunity. This study was undertaken to investigate Pim‐1 and its family members as potential therapeutic targets in early rheumatoid arthritis (RA).MethodsA flow cytometry assay for PIM1 transcript measurement in peripheral blood mononuclear cells from patients with early arthritis was validated and applied as a biomarker of Pim‐1 activity at the cellular level. Synovial protein expression was similarly determined by multiplex immunofluorescence in tissue samples from untreated RA patients and non‐RA disease controls. Functional consequences of Pim kinase family manipulation in freshly isolated CD4+ T cells from these individuals were ascertained, along with the impact of Pim inhibition on mice with collagen‐induced arthritis (CIA).ResultsThe percentage of circulating CD4+ T cells positive for PIM1 transcript by flow cytometry proved a faithful surrogate for gene expression and was significantly higher in patients with early RA than in those with other diseases. Pim‐1 protein levels were similarly up‐regulated in synovial CD4+ T cells from patients with early RA. Ex vivo, exposure of T cell receptor–stimulated early RA CD4+ T cells to Pim kinase inhibitors restrained their activation and proliferative capacity. Diminished production of proinflammatory cytokines (interferon‐γ and interleukin‐17) and an expanded CD25highFoxP3+ Treg cell fraction were also observed in exposed versus unexposed cells. Finally, administration of Pim inhibitors robustly limited arthritis progression and cartilage destruction in CIA.ConclusionOur findings indicate that Pim kinases are plausible therapeutic targets in a readily identifiable subgroup of patients with early RA. Repurposing of Pim inhibitors for this disease should be considered.

项与 MOV10L1 相关的新闻（医药）

2023-10-17

·PRNewswire

In collaboration with leading cancer centers, research results to be presented from seven studies across a breadth of tumor types and genomic alterations demonstrating Caris' impact on precision medicine IRVING, Texas, Oct. 17, 2023 /PRNewswire/ -- Caris Life Sciences®(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, today announced that the company and collaborators within the Caris Precision Oncology Alliance™ (POA) will collectively present seven studies across a breadth of tumor types at the European Society for Medical Oncology (ESMO) Congress 2023 in Madrid, Spain from October 20-24, 2023 (Booth #513). The findings demonstrate the power of Caris' comprehensive clinico-genomic database that enable novel insights into cancer that could have profound effects on a patient's diagnosis, prognosis, care plan and response to treatment. Continue Reading "The research being presented at this year's ESMO Congress is a testament to Caris' continued commitment to data-driven molecular innovation and large-scale collaboration to answer some of the pressing questions in precision oncology today," said Chadi Nabhan, M.D., MBA, FACP, Chairman of the Caris POA. "The findings of these studies illustrate the power of comprehensive molecular profiling to identify underlying tumor biology setting the stage for therapeutics that improve patient outcomes. Alongside our POA partners, we are pioneering new approaches to help deliver the right treatments to the right patients at the right time." Research results to be presented demonstrate Caris Life Sciences' impact on precision medicine Tweet this "More than ever before, our comprehensive molecular profiling coupled with rich clinical data is enabling Caris to help clinicians make the best treatment choices, researchers to discover novel cancer biology, and the biopharmaceutical industry to develop the next breakthrough medicines," said George W. Sledge, Jr., M.D., Executive Vice President and Chief Medical Officer of Caris. "Data presented at this year's ESMO Congress highlight not only our efforts to achieve these goals but also the value of Caris' comprehensive approach to molecular profiling, built on our extensive data, to better understand the biological hallmarks of cancers and ultimately improve outcomes for all cancer patients." Data to be presented by Caris and the POA include the results of a molecular analysis of more than 278,000 tumors that indicate potential new therapeutic opportunities in gastrointestinal cancers. Other notable topics explored in these abstracts include a real-world data analysis of gene expression and outcomes in breast cancer, exploration of the tumor-immune microenvironment in lung cancer, and genomic and immune profiling of patients with a rare and aggressive form of eye cancer: Therapeutic opportunities for Porcupine inhibition in Gastrointestinal cancer (Abstract Number: 222P) October 21, 2023 An Analysis of Proviral Insertion Site of Moloney Murine Leukemia Virus 1 Kinase Expression (PIM1) and Clinical Outcomes in Advanced Breast Cancer (ABC) (Abstract Number: 494P) October 21, 2023 Multi-omics evaluation of TFE3-fusions and potential association with immuno-metabolic vulnerabilities in alveolar soft part sarcoma (ASPS) and translocation-positive renal cell carcinoma (tRCC) (Abstract Number: 2281P) October 21, 2023 Landscape of Delta-like-ligand 3 (DLL3) expression across neuroendocrine neoplasms (NENs) (Abstract Number: 1188P) October 22, 2023 Chemokine expression in uveal melanoma and association with tumor genetics and response to immunotherapy (Abstract Number: 1132P) October 22, 2023 STAT3, ACTA2, and SPARC stromal markers predict response to Gemcitabine/Cisplatin/Nab-paclitaxel (GCN) in patients with advanced pancreatic adenocarcinoma (aPDAC) (Abstract Number: 1645P) October 23, 2023 Tumor-immune microenvironment analysis of de novo and acquired KRAS-mutated non-small cell lung cancer (Abstract Number: 1399P) October 23, 2023 Abstract summaries of this research will be available onsite at Caris' booth #513. The full abstracts are available through the official ESMO website. The POA includes 89 cancer centers, academic institutions, research consortia and healthcare systems. These institutions have early access to the extensive database and artificial intelligence platform within Caris to establish evidence-based standards for cancer profiling and molecular testing in oncology. By leveraging the comprehensive genomic, transcriptomic and proteomic profiling available through Caris molecular profiling, Caris seeks to provide this network with the ability to prioritize therapeutic options and determine which clinical trial opportunities may benefit their patients. POA members are also able to integrate with a growing portfolio of biomarker-directed trials sponsored by biopharma. Additionally, POA member institutions have access to the most comprehensive clinico-genomic database in the industry, which includes matched molecular and clinical outcomes data from hundreds of thousands of cancer patients, covering over 1 million data points per patient. About Caris Life Sciences Caris Life Sciences® (Caris) is the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, clinico-genomic database and computing capability needed to analyze and unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides an unmatched platform to deliver the next-generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media Contact: Lisa Burgner [email protected] 214.294.5606 SOURCE Caris Life Sciences

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