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TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV

ABSTRACT: TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV

PROVIDER: PRJNA764513 | ENA |

REPOSITORIES: ENA

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TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV

Project description:The Human Silencing Hub (HUSH) complex constituted of TASOR, MPP8 and Periphilin is involved in the spreading of H3K9me3 repressive marks across genes and transgenes such as ZNF encoding genes, ribosomal DNAs, retroelements, including LINE-1 elements, or the integrated HIV provirus. The deposit of these repressive marks leads to heterochromatin formation and inhibits gene expression. The precise mechanisms of HUSH-mediated silencing are still poorly understood, but HUSH presents structural homology with the RNA-induced transcriptional silencing (RITS) complex found in fission yeast. During transcription elongation by RNA polymerase II, RITS recruits a TRAMP-like RNA degradation complex composed of CNOT1 partners, MTR4 and the exosome, to ultimately repress gene expression via H3K9me3 deposit. Here, we show that TASOR depletion or HIV-2 Vpx expression, which induces TASOR degradation, increases the accumulation of transcripts derived from the HIV-1 LTR promoter at a post-transcriptional level. Furthermore, using a yeast 2-hybrid screen, we identified new TASOR partners involved in RNA metabolism including the RNA deadenylase CCR4-NOT complex scaffold CNOT1. TASOR and CNOT1 interact in vivo and synergistically repress HIV expression from its LTR. Similar to the RITS complex, we show that TASOR interacts and cooperates with MTR4 and the exosome. We also highlight an interaction between TASOR and RNA Polymerase II, predominantly under its elongating state, and between TASOR and some HUSH-targeted nascent transcripts. Finally, we show that TASOR overexpression facilitates the association of the aforementioned RNA degradation proteins with RNA polymerase II and is detected at transcriptional centers. Altogether, we propose that HUSH operates at the transcriptional and post-transcriptional levels to repress HIV proviral gene expression.

2021-11-11 | GSE184399 | GEO

TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV.

Project description: Not available

| S-EPMC8748822 | biostudies-literature

Ribosome Profiling with CNOT1 depletion

Project description:Ribosome profiling in HEK293 cells with and without the depletion of CNOT1. This allows the determination of translational efficiency and nucleotide resolution of ribosome occupancy.

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The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes

Project description:The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes

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mRNA stability experiments with control or CNOT1-targeting siRNA treatment in HEK293 cells

Project description:Determination of mRNA half-life in HEK293 cells with and without the depletion of CNOT1.

2021-08-22 | GSE158619 | GEO

Ribosome Profiling with CNOT1 depletion

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CNOT1 and Transcriptomic Landscape of a HeLa Cell Line

Project description:Purpose: The goals of this study are to compare NGS-derived total transcriptome profiling (RNA-seq) of CNOT1-depleted cells (using siRNA) with control HeLa cells before and after DNA damage to examine quantitative gene expression.

2019-12-05 | GSE141496 | GEO

The E2F4/p130 repressor complex cooperates with oncogenic DNp73a to promote cell survival

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RNA-seq of ER-targeted and cytosolic mRNAs with control or CNOT1-targeting siRNA treatment in HEK293 cells

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Knockout of CNOT1 and CNOT10 in primary CD4+ T-cells causes a type-1 interferon response

Project description:We report a type 1 interferon response accompanying polyclonal knockout of CNOT1 or CNOT10 in primary human CD4+ T-cells harvested from healthy donors

2020-01-24 | GSE144142 | GEO

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