mRNA export protein THOC5 as a tool for identification of target genes for cancer therapy

Tran, Doan Duy Hai; Saran, Shashank; Koch, Alexandra; Tamura, Teruko

doi:10.1016/j.canlet.2016.01.045

Cited by 14 publications

(12 citation statements)

References 34 publications

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“…Human TREX functions in transcription and mRNA processing and export ( 4 , 15 ). In addition, TREX is also important for embryogenesis, organogenesis as well as cellular differentiation and implicated in several diseases ( 15 , 33 ). The subunit composition of the TREX complex in Drosophila is similar to the human one ( 34 ).…”

Section: Introductionmentioning

confidence: 99%

Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes

Minocha

Popova

Копытова

et al. 2018

Nucleic Acids Research

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The different steps of gene expression are intimately linked to coordinate and regulate this complex process. During transcription, numerous RNA-binding proteins are already loaded onto the nascent mRNA and package the mRNA into a messenger ribonucleoprotein particle (mRNP). These RNA-binding proteins are often also involved in other steps of gene expression than mRNA packaging. For example, TREX functions in transcription, mRNP packaging and nuclear mRNA export. Previously, we showed that the Prp19 splicing complex (Prp19C) is needed for efficient transcription as well as TREX occupancy at transcribed genes. Here, we show that the splicing factor Mud2 interacts with Prp19C and is needed for Prp19C occupancy at transcribed genes in Saccharomyces cerevisiae. Interestingly, Mud2 is not only recruited to intron-containing but also to intronless genes indicating a role in transcription. Indeed, we show for the first time that Mud2 functions in transcription. Furthermore, these functions of Mud2 are likely evolutionarily conserved as Mud2 is also recruited to an intronless gene and interacts with Prp19C in Drosophila melanogaster. Taken together, we classify Mud2 as a novel transcription factor that is necessary for the recruitment of mRNA-binding proteins to the transcription machinery. Thus, Mud2 is a multifunctional protein important for transcription, splicing and most likely also mRNP packaging.

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Section: Introductionmentioning

confidence: 99%

Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes

Minocha

Popova

Копытова

et al. 2018

Nucleic Acids Research

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“…Abnormal expression of THOCs induced abnormal cell cycle and cell proliferation in tumor. 32 THOC1 played a role in activating G2/M cell cycle checkpoint. 33 THOC4 was involved in the regulation of S and G2 cell cycle, which may be related to the effect of THOC4 on the expression of cyclins.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma

Li¹,

Liu²,

Wei³

et al. 2022

IJGM

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Background THO complex members (THOCs) are essential for mRNA processing, transcription elongation, mRNA export and genome integrity, which may be associated with tumor. However, the significance of THO complex members in Hepatocellular carcinoma (HCC) has not been clarified. Methods In this study, we investigated expression levels, clinicopathological correlation, diagnostic and prognostic value, disease associations, co-expression network, functional enrichment, genetic variation, drug sensitivity, molecular targets, and immune infiltration of THOCs in HCC using UALCAN, ICGC, HPA, Kaplan–Meier Plotter, The Open Targets Platform database, GeneMANIA, WebGestalt, GSCALite, LinkedOmics, TIMER. Meanwhile, the mRNA expression levels of THOCs in HCC were verified by qRT-PCR. Results THOCs were significantly up-regulated at the transcription level in HCC, and overexpression of THOCs was correlated with clinicopathological features. THOCs had potential diagnostic and prognostic value for HCC. THOCs could participate in apoptosis, regulate cell cycle, and were also involved in DNA damage response. Important cancer-related signaling pathways such as EMT, RAS/MAPK pathway and RKT pathway were also related to THOCs expression. In addition, the expression level of THOC1/2/6/7 was negatively correlated with drug resistance. And miRNA, kinase, and transcription factor targets associated with THOCs have been identified. Meanwhile, THOCs were associated with immune infiltration in HCC. Conclusion Our study revealed that THO complex members have important clinical significance for HCC and have potential clinical utility in diagnosis, treatment and prognosis.

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“…THOC1 has previously been associated to prostate cancer aggressiveness [ 39 ]. THOC5 is highly specialised in the processing of mRNAs related to cancer proliferation, since it contributes to more than 90% of the 3′ processing and/or export of immediate-early genes induced by growth factors and/or cytokines, but only to less than 1% of total mRNA export in the steady state [ 40 , 41 ]. This reinforces our hypothesis that HMGB1 interactions orchestrate the transcription of specific pre-rRNAs and pre-mRNAs to their processing, nucleo-cytoplasmic export and final participation in translation.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes

Barreiro-Alonso

Lamas-Maceiras

Lorenzo-Catoira

et al. 2021

Cancers

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This study reports the HMGB1 interactomes in prostate and ovary cancer cells lines. Affinity purification coupled to mass spectrometry confirmed that the HMGB1 nuclear interactome is involved in HMGB1 known functions such as maintenance of chromatin stability and regulation of transcription, and also in not as yet reported processes such as mRNA and rRNA processing. We have identified an interaction between HMGB1 and the NuRD complex and validated this by yeast-two-hybrid, confirming that the RBBP7 subunit directly interacts with HMGB1. In addition, we describe for the first time an interaction between two HMGB1 interacting complexes, the septin and THOC complexes, as well as an interaction of these two complexes with Rab11. Analysis of Pan-Cancer Atlas public data indicated that several genes encoding HMGB1-interacting proteins identified in this study are dysregulated in tumours from patients diagnosed with ovary and prostate carcinomas. In PC-3 cells, silencing of HMGB1 leads to downregulation of the expression of key regulators of ribosome biogenesis and RNA processing, namely BOP1, RSS1, UBF1, KRR1 and LYAR. Upregulation of these genes in prostate adenocarcinomas is correlated with worse prognosis, reinforcing their functional significance in cancer progression.

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mRNA export protein THOC5 as a tool for identification of target genes for cancer therapy

Cited by 14 publications

References 34 publications

Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes

Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes

Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma

HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes

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