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Transcriptomic analysis of TDRD9-depleted lung tumor cells

ABSTRACT: Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline. We have shown that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas. Here we determine the transcriptomic changes of a TDRD9-positive lung tumor cells line (NCI-H1993) depleted of TDRD9.

ORGANISM(S): Homo sapiens

PROVIDER: GSE104151 | GEO | 2018/09/23

REPOSITORIES: GEO

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Defective RNA helicase genes underlie predisposition to colorectal and hematological malignancies

Project description:Background: Causative genes are mostly unknown for the mismatch repair-proficient category of familial colorectal cancers designated as FCCTX. Recent evidence suggests shared susceptibility factors between colorectal and hematological malignancies. Study design: We investigated 28 FCCTX families by exome sequencing, supplemented with whole genome sequencing, RNA-sequencing, and tumor studies to identify the predisposing genes. Guided by the findings, germline and somatic exomes of ~400 patients with acute leukemia, myelodysplastic syndrome, and myeloma were subsequently examined. Results: A family with hematological and solid malignancies revealed a truncating variant in the DEAH-box RNA helicase gene DHX40 co-segregating with disease in seven family members. Neoplastic tissues revealed no apparent “second hit”, implying a haploinsufficiency model of tumorigenesis. DHX40 siRNA-treated cell lines exhibited a 13% increase in aberrantly spliced transcripts vs. GAPDH-siRNA or non-target siRNA-treated cells. Two additional families showed truncating germline variants in the TDRD9 and TDRD5 genes encoding Tudor domain-containing RNA-binding proteins. In the hospital-based hematological series, 18% of germline and 28% of somatic exomes revealed possibly pathogenic DEAD/H box gene variants, including somatic variants of DHX40 in four. Conclusions: This study identifies DHX40, TDRD9, and TDRD5 as novel candidate genes for FCCTX predisposition. In the family segregating the truncating DHX40 variant, two carriers had hematological neoplasia, suggesting possible analogy to DDX41, a DEAD-box RNA helicase gene previously linked to myeloid malignancies. Our findings emphasize aberrant RNA metabolism behind FCCTX and hematological neoplasia.

2023-11-08 | GSE228991 | GEO

Transcriptomic analysis of TDRD9-depleted lung tumor cells

Project description:Transcriptomic analysis of TDRD9-depleted lung tumor cells

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Transcriptomic analysis of tudor[1] mutant Drosophila brain and ovaries

Project description:In Drosophila, Tudor protein and its germline partners, Piwi proteins, are expressed in the brain. However, the potential significance of Tudor in neurobiology has not been explored. Here, we test a hypothesis that Tudor is an essential regulator of post-transcriptional gene expression in the brain where it controls levels of certain RNAs required for brain functions. Specifically, transcriptome of tudor mutant brains is compared with that of wild-type brains using next-generation sequencing (RNA-Seq). The hypothesis that Tudor regulates the same genes in both brain and germline is tested by comparing the transcriptomes from tudor mutant brains and ovaries. This research aims at providing innovative outcomes which may reveal exciting commonalities between the germline and brain and may contribute to our understanding of neurodegenerative disorders and the mechanisms of learning and memory.

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C. elegans small RNA-seq profiling of three different lotr-1 mutant alleles

Project description:Proteins containing LOTUS and Tudor domains have critical roles in the germline, including in small RNA biology. LOTR-1 is the only protein expressed in the germline of C. elegans which has LOTUS and Tudor domains. Here, to understand the influence of LOTR-1 in small RNA biology, we sequenced small RNAs of wild-type and lotr-1 mutant animals.

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The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline

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UPF1 helicase promotes Tudor-SN-mediated miRNA decay

Project description:The helicase activity of UPF1 remodels miRNPs so as to render miRNAs susceptible to Tudor-SN (TSN)-mediated miRNA decay

2017-08-22 | GSE100068 | GEO

RNA clamping by Vasa assembles a piRNA Amplifier complex on transposon transcripts

Project description:Germline-specific Piwi-interacting RNAs (piRNAs) protect the genome against selfish genetic elements and are essential for fertility in animals. piRNAs targeting active transposons are amplified by a feed-forward loop known as the Ping-pong cycle, which links endonucleolytic slicing of target RNAs by Piwi proteins to biogenesis of new piRNAs. However, the biochemical framework for this pathway remains elusive. Here, we describe the identification of a transient Amplifier complex mediating the biogenesis of secondary piRNAs in insect cells. This complex is nucleated by the RNA helicase Vasa and contains the two Piwi proteins participating in the Ping-pong loop, the Tudor protein Qin/Kumo and antisense piRNA guides. These components assemble on the surface of Vasa's helicase domain, which functions as an RNA clamp to anchor Amplifier onto transposon transcripts. We show that ATP-dependent RNP remodelling by Vasa facilitates the transfer of 5'-sliced piRNA precursors between the Ping-pong partners, and failure to achieve this results in Drosophila female sterility. Immunoprecipitated small RNA were purified from untransfected or transfected Bmn4 cells for preparation of high-throughput sequencing libraries.

2014-06-04 | E-GEOD-57420 | biostudies-arrayexpress

Homo sapiens

Project description:UPF1 helicase promotes Tudor-SN-mediated miRNA decay

| PRJNA390626 | ENA