Post-transcriptional Inhibition of Gene Expression: Sense and Antisense Genes

1994 ◽  
pp. 309-334 ◽  
Author(s):  
Joseph N. M. Mol ◽  
Rik Van Blokland ◽  
Pieter De Lange ◽  
Maike Stam ◽  
Jan M. Kooter
Keyword(s):  
Gene Expression ◽  
Transcriptional Inhibition ◽  
Antisense Genes

scholarly journals Interaction of 7SK with the Smn complex modulates snRNP production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Changhe Ji ◽  
Jakob Bader ◽  
Pradhipa Ramanathan ◽  
Luisa Hennlein ◽  
Felix Meissner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Fine Tuning ◽  
Global Changes ◽  
Functional Association ◽  
Transcriptional Inhibition ◽  
Smn Complex ◽  
Core Components

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

scholarly journals Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes: transcriptional inhibition by interferon-γ

1995 ◽  
Vol 310 (3) ◽  
pp. 751-755 ◽  
Author(s):  
M A Cassatella ◽  
S Gasperini ◽  
F Calzetti ◽  
P P McDonald ◽  
G Trinchieri
Keyword(s):  
Gene Expression ◽  
Interferon Γ ◽  
Interleukin 8 ◽  
Polymorphonuclear Leucocytes ◽  
Mrna Accumulation ◽  
Ifn Gamma ◽  
Potent Inducer ◽  
Transcriptional Inhibition ◽  
Human Granulocytes ◽  
New Protein

We recently showed that lipopolysaccharide (LPS) is a potent inducer of interleukin-8 (IL-8) expression in human polymorphonuclear leucocytes (PMN), at the level of both mRNA and protein, and that interferon-gamma (IFN gamma) inhibits IL-8 mRNA accumulation in stimulated PMN. To further define the molecular basis of the regulation of IL-8 gene expression in PMN, we investigated the effects of LPS and IFN gamma at both the transcriptional and post-transcriptional levels. As determined by Northern blot analysis, new protein synthesis was not required for the induction of IL-8 mRNA expression by LPS. Neither did the half-life of IL-8 mRNA in LPS-treated PMN differ from that observed in untreated cells. However, nuclear run-on analysis revealed that LPS increased the transcription of the IL-8 and IL-1 beta genes and that, in LPS-activated cells, IFN gamma markedly inhibited the rate of IL-8 gene transcription, but not that of IL-1 beta. IFN gamma did not affect IL-8 mRNA stability in LPS-treated PMN, indicating that the cytokine does not regulate LPS-induced IL-8 gene expression through post-transcriptional events. These results provide the first evidence that human granulocytes can actively transcribe the IL-8 gene, and that transcriptional inhibition is the mechanism by which IFN gamma inhibits IL-8 gene expression in PMN.

PS2-062. Novel role of IRF5 in transcriptional inhibition of human IL-10 gene expression

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 81
Author(s):  
Thomas Krausgruber ◽  
David Saliba ◽  
Hayley Eames ◽  
Lynn Williams ◽  
Tim Smallie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Inhibition

scholarly journals RNA interactions with CTCF are essential for its proper function

2019 ◽  
Author(s):  
Ricardo Saldaña-Meyer ◽  
Javier Rodriguez-Hernaez ◽  
Mayilaadumveettil Nishana ◽  
Karina Jácome-López ◽  
Elphege P. Nora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ctcf Binding ◽  
Proper Function ◽  
List Type ◽  
Transcriptional Inhibition ◽  
Local Insulation

SummaryThe function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms of how CTCF dynamically contributes to genome organization is not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs; promoting its oligomerization. Here we found that inhibition of transcription or interfering with CTCF ability to bind RNA through mutations of two of its 11 zinc fingers that are not involved with CTCF binding to its cognate site in vitro, zinc finger-1 (ZF1) or −10 (ZF10), disrupt CTCF association to chromatin. These mutations alter gene expression profiles as CTCF mutants lose their ability to promote local insulation. Our results highlight the importance of RNA as a structural component of the genome, in part by affecting the association of CTCF with chromatin and likely its interaction with other factors.Transcriptional inhibition disrupts CTCF binding to chromatinRNA-binding regions (RBR) in CTCF are found within ZF1 and ZF10Local insulation is markedly decreased in ZF1∆ and ZF10∆ mutant rescuesGene expression and chromatin organization are disrupted by RBR mutants

scholarly journals An improved CRISPR/dCas9 interference tool for neuronal gene suppression

2020 ◽  
Author(s):  
Corey G. Duke ◽  
Svitlana V. Bach ◽  
Jasmin S. Revanna ◽  
Faraz A. Sultan ◽  
Nicholas T. Southern ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Expression System ◽  
Genetic Material ◽  
Gene Promoters ◽  
Disease States ◽  
Transcriptional Inhibition ◽  
Health And Disease ◽  
Neuronal Systems ◽  
And Function

The expression of genetic material governs brain development, differentiation, and function, and targeted manipulation of gene expression is required to understand contributions of gene function to health and disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled targeted transcriptional repression at selected genomic sites, integrating these techniques for use in non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus expression system to express CRISPR-based activation machinery in post-mitotic neurons. Here we used a similar strategy to adapt an improved dCas9-KRAB-MeCP2 repression system for robust transcriptional inhibition in neurons. We find that lentiviral delivery of a dCas9-KRAB-MeCP2 construct driven by the neuron-selective promoter human synapsin 1 enabled transgene expression in primary rat neurons. Next, we demonstrate transcriptional repression using CRISPR sgRNAs targeting diverse gene promoters, and show superiority of this system in neurons compared to existing RNA interference methods for robust transcript specific manipulation at the complex Brain-derived neurotrophic factor (Bdnf) gene. Our findings advance this improved CRISPRi technology for use in neuronal systems for the first time, potentially enabling improved ability to manipulate gene expression states in the nervous system.

scholarly journals CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from α-Defensin-1 HIV Inhibition

2003 ◽  
Vol 77 (12) ◽  
pp. 6777-6784 ◽  
Author(s):  
Theresa Li-Yun Chang ◽  
Fleur François ◽  
Arevik Mosoian ◽  
Mary E. Klotman
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
Viral Entry ◽  
Neutralizing Antibody ◽  
Inhibitory Effect ◽  
Transcriptional Inhibition ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT CD8+ T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8+ T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that α-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether α-defensins, particularly α-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant α-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8+ cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with α-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, α-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, α-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8+ cells with potent HIV-1 inhibitory activity and a neutralizing antibody against α-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that α-defensin-1 inhibits HIV-1 infection following viral entry but that α-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.

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