Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation

Cloutier, Sara C.; Wang, Siwen; Kit, Wai; Husini, Nadra Al; Dhoondia, Zuzer; Ansari, Athar; Pascuzzi, Pete E.; Tran, Elizabeth

doi:10.1016/j.molcel.2016.03.012

Cited by 28 publications

(25 citation statements)

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“…Moreover, we found that DDX5/DDX17 depletion increased the amount of XRN2, CstF64 and THOC5 associated with the pause site of the HSPA1A gene concomitant with an increase in the amount of read‐through transcript, the latter of which is a hallmark of transcriptional termination defect. Interestingly, Dbp2, a yeast ortholog of DDX5/DDX17, has also been implicated in the control of R‐loop formation and transcription termination process (Cloutier, Ma, Nguyen, & Tran, ; Cloutier et al, ). Thus, our data indicate that the conserved RNA helicases carry out similar roles in gene expression in mammals and that the steps in which they participate are most likely transcriptional termination, recycling of these factors and subsequent transcript release.…”

Section: Discussionmentioning

confidence: 99%

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

et al. 2019

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A multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the HSPA1A gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked HSP70 transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for HSP70 transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of HSP70 transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the HSPA1A locus.

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Section: Discussionmentioning

confidence: 99%

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

et al. 2019

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“…The DDX5/Dbp2 subfamily (orange circles, “DEAD”) functions as RNP chaperones in a variety of processes. This includes regulation of lncRNA activities (Cloutier et al, ; Yao et al, ; Zhang et al, ), pre‐mRNA splicing (Z.‐R. Liu, ), alternative splicing (Y. J. Lee, Wang, & Rio, ), mRNA export (Ma et al, ), miRNA processing (Remenyi, Bajan, Fuller‐Pace, Arthur, & Hutvagner, ), nonsense‐mediated decay (NMD) (Geißler, Altmeyer, Stein, Uhlmann‐Schiffler, & Stahl, ), and ribosome biogenesis (Saporita et al, )…”

Section: Functions Of the Ddx5/dbp2 Subfamily In Rna Metabolism And Gmentioning

confidence: 99%

“…In the presence of glucose, the preferred carbon source for yeast, the GAL genes are shut off transcriptionally. While the GAL genes are repressed, the GAL lncRNAs are expressed and form RNA/DNA hybrids (R‐loops) with the genomic DNA (Cloutier et al, , ). R‐loops are generated by base paring of an RNA molecule to one strand of the genomic DNA, leaving the other strand free.…”

Section: Functions Of the Ddx5/dbp2 Subfamily In Rna Metabolism And Gmentioning

confidence: 99%

“…R‐loops are generated by base paring of an RNA molecule to one strand of the genomic DNA, leaving the other strand free. The GAL R‐loops prepare the GAL genes for faster induction during a nutritional switch to glucose‐depleted, galactose‐containing media (Cloutier et al, ; Cloutier, Wang, Ma, Petell, & Tran, ). Dbp2 antagonizes the function of the GAL lncRNAs: deletion of DBP2 promotes the GAL lncRNA R‐loop formation, thereby displacing transcriptional repressors and speeding up transcriptional activation (Cloutier et al, ).…”

Section: Functions Of the Ddx5/dbp2 Subfamily In Rna Metabolism And Gmentioning

confidence: 99%

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The DDX5/Dbp2 subfamily of DEAD‐box RNA helicases

2018

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The mammalian DEAD-box RNA helicase DDX5, its paralog DDX17, and their orthologs in Saccharomyces cerevisiae and Drosophila melanogaster, namely Dbp2 and Rm62, define a subfamily of DEAD-box proteins. Members from this subfamily share highly conserved protein sequences and cellular functions. They are involved in multiple steps of RNA metabolism including mRNA processing, microRNA processing, ribosome biogenesis, RNA decay, and regulation of long non-coding RNA activities. The DDX5/Dbp2 subfamily is also implicated in transcription regulation, cellular signalling pathways, and energy metabolism. One emerging theme underlying the diverse cellular functions is that the DDX5/Dbp2 subfamily of DEAD-box helicases act as chaperones for complexes formed by RNA molecules and proteins (RNP) in vivo. This RNP chaperone activity governs the functions of various RNA species through their life time. Importantly, mammalian DDX5 and DDX17 are involved in cancer progression when overexpressed through alteration of transcription and signalling pathways, meaning that they are possible targets for cancer therapy.

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“…Long noncoding RNAs (lncRNAs), which are defined as endogenous, cellular, protein-noncoding RNAs more than 200 nucleotides in length, have been shown to play important roles in gene expression regulation and various aspects of tumor cellular homeostasis, including tumor cell proliferation, differentiation, apoptosis, and metastasis [3]. Long intergenic noncoding RNA 152 (LINC00152), a lncRNA whose gene is located in chromosome region 2p11.2, was first identified in gastric cancer and shows significantly increased expression in cancer tissues and cells [4].…”

Section: Introductionmentioning

confidence: 99%

Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

Chen¹,

Li²,

Gao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are a novel class of protein-noncoding transcripts that are aberrantly expressed in multiple diseases including cancers. LINC00152 has been identified as an oncogene involved in many kinds of cancer; however, its expression pattern and function in human glioma remain unclear. Methods: Quantitative real-time polymerase chain reaction was carried out to measure LINC00152 expression in human glioma cell lines and tissues. CCK-8 and EdU assays were performed to assess cell proliferation, and scratch assays and Transwell assays were used to assess cell migration and invasion, respectively. Luciferase reporter assays were carried out to determine the interaction between miR-16 and LINC00152. In vivo experiments were conducted to assess tumor formation. Results: LINC00152 was found to be significantly upregulated in human glioma cell lines and clinical samples. Knockdown of LINC00152 suppressed glioma cell proliferation, migration, and invasion in vitro. In vivo assays in nude mice confirmed that LINC00152 knockdown inhibits tumor growth. Furthermore, mechanistic investigation showed that LINC00152 binds to miR-16 in a sequence-specific manner and suppresses its expression. miR-16 inhibition strongly attenuated LINC00152 knockdown–mediated suppressive effects on proliferation, migration, and invasion. Moreover, LINC00152 induced BMI1 expression by sponging miR-16; this effect further promoted glioma cell proliferation and invasion. Conclusion: We regard LINC00152 as an oncogenic lncRNA promoting glioma cell proliferation and invasion and as a potential target for human glioma treatment.

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Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation

Cited by 28 publications

References 0 publications

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

The DDX5/Dbp2 subfamily of DEAD‐box RNA helicases

Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

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