The THO complex is required for stress tolerance and longevity in Drosophila

Kim, Hyeun; Cho, Bongki; Moon, Sungjin; Chung, Yun Doo

doi:10.1007/s13258-011-0049-6

Cited by 8 publications

(10 citation statements)

References 26 publications

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“…It has been well established that PI3K/AKT signaling pathway is a key player in regulating life span as well as body size in Drosophila (Edgar, 2006). Combined with the previously reported lifespan reduction (Kim et al, 2011), increased body size in the THO mutant flies compared to control is well matched with the known phenotypes of mutant flies with defects in PI3K/AKT signaling pathway (Edgar, 2006). Although we failed to detect a global increase in PI3K/AKT signaling in the THO mutant flies (Supplementary Fig.…”

Section: Discussionsupporting

confidence: 78%

“…In the previous report, we showed the reduced life span and the increased susceptibility to the environmental stresses in mutant flies for Drosophila THO subunits (Kim et al, 2011). To understand the underlying mechanisms of these defects, here we investigated genetic interactions of THO with 2 cellular signaling pathways, p53 and PI3K/AKT pathways.…”

Section: Discussionmentioning

confidence: 92%

“…Previously, we reported that thoc5 flies were viable but showed severe defects in the spermatocytes including meiotic arrest and nucleolar disruption . In addition to this, THO dysfunction in Drosophila could cause a significant shortening of life span as well as increased sensitivity to the environmental stresses (Kim et al, 2011). To understand the underlying mechanisms for these phenotypes, here we examined 2 cellular signaling pathways, p53 and PI3K/AKT pathways, which have been well known to play important roles in cell differentiation and in cellular stress responses.…”

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confidence: 99%

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p53 and PI3K/AKT Signalings Are Up-Regulated in Flies with Defects in the THO Complex

Moon

Chung

2013

Molecules and Cells

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The THO complex (THO) is an evolutionary conserved protein required for the formation of export-competent mRNP. The growing evidence indicates that the metazoan THO plays important roles in cell differentiation and cellular stress response. But the underlying mechanisms are poorly understood. Herein we examined the relevance of THO to cellular signaling pathways involved in cell differentiation and cellular stress response. When we examined the endogenous p53 level in the testis, it was sustained much longer during spermatogenesis in the THO mutant compared to that of wild-type. In flies with impaired THO, overexpression of p53 by eye-specific GAL4 not only enhanced p53-mediated retinal degeneration, but p53 level was also elevated compared to the control flies. Since the body size of the THO mutant flies was significantly larger than control flies, we also examined whether the PI3K/AKT signaling is enhanced in the mutant flies. The results showed that the endogenous level of phosphorylated AKT, which is the active form, was highly elevated in the THO mutants. Taken together our results suggested that both p53 and PI3K/AKT signalings are up-regulated in the flies with impaired THO. INTRODUCTIONThe eukaryotic gene expression requires complex regulation at various stages. The THO complex (THO) participates in the eukaryotic gene expression at the interface between transcription and RNA export. THO was first discovered as a protein complex that connects transcription elongation with mitotic recombination in budding yeast (Chávez et al., 2000). Subsequent studies have revealed that THO is involved in forming an optimal mRNP for nuclear export, preventing the nascent RNA from interacting with the DNA template (Jimeno et al., 2002). Metazoans also have a functional homolog of THO, although their subunit composition is slightly different from that of budding yeast (Masuda et al., 2005;Rehwinkel et al., 2004). Metazoan THO consists of 5 subunits, THOC1/HPR1, THOC2/ THO2, THOC5, THOC6 and THOC7. Now, it is clear that THO is required for the biogenesis of export-competent mRNPs at the single cell level (review by Jimeno and Aguilera, 2010).However, our understanding of THO function at the multicellular organism level is very limited. Several lines of recent evidence have suggested that metazoan THO has cell type-specific roles during development (Griaud et al., 2012;Kopytova et al., 2010;Mancini et al., 2010;Moon et al., 2011;Wang et al., 2009). In mice homozygous for a hyphomorphic Thoc1 allele, spermatogenesis was severely compromised due to defects in the expression of genes required for normal cell differentiation in the testis, while most other tissues appeared to be unaffected (Wang et al., 2009). Using conditional knock-out mice, Mancini et al. (2010) showed that THOC5 was an essential element in the maintenance of hematopoiesis, whereas it was less important in differentiated cell types such as hepatocytes and heart muscles. In addition, it has been shown that THOC1 was differentially expressed in human cancers; i...

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

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p53 and PI3K/AKT Signalings Are Up-Regulated in Flies with Defects in the THO Complex

Moon

Chung

2013

Molecules and Cells

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“…and Y.D.C., unpublished). Our recent work also showed that longevity and tolerance to environmental stress were significantly reduced in the THO mutants (Kim et al, 2011). This suggests that the role of the THO complex is not limited to spermatogenesis, but is also important for other types of cells.…”

Section: Research Articlementioning

confidence: 68%

“…Primary antibodies used in this study were: anti-THOC7 (Kim et al, 2011) at 1:1000, anti-HPR1 (Rehwinkel et al, 2004) at 1:100, anti-THO2 (Rehwinkel et al, 2004) at 1:100, anti-THOC5 (Kopytova et al, 2010) at 1:100 and anti-Fibrillarin (38F3; Santa Cruz, sc-56676) at 1:50. The secondary antibodies Alexa 546-conjugated goat anti-rabbit (1:500) and Alexa 488-conjugated goat anti-mouse (1:500) were purchased from Molecular Probes.…”

Section: Antibody Staining and Microscopymentioning

confidence: 99%

The THO complex is required for nucleolar integrity in Drosophila spermatocytes

et al. 2011

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SUMMARYThe THO complex is a conserved multisubunit protein complex that functions in the formation of export-competent messenger ribonucleoprotein (mRNP). Although the complex has been studied extensively at the single-cell level, its exact role at the multicellular organism level has been poorly understood. Here, we isolated a novel Drosophila male sterile mutant, garmcho (garm). Positional cloning indicated that garm encodes a subunit of the Drosophila THO complex, THOC5. Flies lacking THOC5 showed a meiotic arrest phenotype with severe nucleolar disruption in primary spermatocytes. A functional GFP-tagged fusion protein, THOC5-GFP, revealed a unique pattern of THOC5 localization near the nucleolus. The nucleolar distribution of a testisspecific TATA binding protein (TBP)-associated factor (tTAF), SA, which is required for the expression of genes responsible for sperm differentiation, was severely disrupted in mutant testes lacking THOC5. But THOC5 appeared to be largely dispensable for the expression and nuclear export of either tTAF target mRNAs or tTAF-independent mRNAs. Taken together, our study suggests that the Drosophila THO complex is necessary for proper spermatogenesis by contribution to the establishment or maintenance of nucleolar integrity rather than by nuclear mRNA export in spermatocytes.

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Co-dependent Assembly of Drosophila piRNA Precursor Complexes and piRNA Cluster Heterochromatin

Zhang

et al. 2018

Cell Reports

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In Drosophila, the piRNAs that guide germline transposon silencing are produced from heterochromatic clusters marked by the HP1 homolog Rhino. We show that Rhino promotes cluster transcript association with UAP56 and the THO complex, forming RNA-protein assemblies that are unique to piRNA precursors. UAP56 and THO are ubiquitous RNAprocessing factors, and null alleles of uap56 and the THO subunit gene tho2 are lethal. However, uap56sz15 and mutations in the THO subunit genes thoc5 and thoc7 are viable but sterile and disrupt piRNA biogenesis. The uap56sz15 allele reduces UAP56 binding to THO, and the thoc5 and thoc7 mutations disrupt interactions among the remaining THO subunits and UAP56 binding to the core THO subunit Hpr1. These mutations also reduce Rhino binding to clusters and trigger Rhino binding to ectopic sites across the genome. Rhino thus promotes assembly of piRNA precursor complexes, and these complexes restrict Rhino at cluster heterochromatin.

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The THO complex is required for stress tolerance and longevity in Drosophila

Cited by 8 publications

References 26 publications

p53 and PI3K/AKT Signalings Are Up-Regulated in Flies with Defects in the THO Complex

p53 and PI3K/AKT Signalings Are Up-Regulated in Flies with Defects in the THO Complex

The THO complex is required for nucleolar integrity in Drosophila spermatocytes

Co-dependent Assembly of Drosophila piRNA Precursor Complexes and piRNA Cluster Heterochromatin

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