Modulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells

Vijayakumar, Aarthi; Park, Annsea; Steitz, Joan A.

doi:10.3389/fimmu.2022.828665

Cited by 8 publications

(5 citation statements)

References 71 publications

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“… Identified CPA factors implicated in pre-mRNA 3′ end processing. Eukaryotic mRNA 3′ end processing is a multi-step process ( 126 , 127 ). In this study, we identified a variety of CPA factors implicated in multiple steps of 3′ end processing.…”

Section: Resultsmentioning

confidence: 99%

Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter

Ni,

Ahmed,

Nabeel-Shah

et al. 2024

Nucleic Acids Research

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Messenger RNA precursors (pre-mRNA) generally undergo 3′ end processing by cleavage and polyadenylation (CPA), which is specified by a polyadenylation site (PAS) and adjacent RNA sequences and regulated by a large variety of core and auxiliary CPA factors. To date, most of the human CPA factors have been discovered through biochemical and proteomic studies. However, genetic identification of the human CPA factors has been hampered by the lack of a reliable genome-wide screening method. We describe here a dual fluorescence readthrough reporter system with a PAS inserted between two fluorescent reporters. This system enables measurement of the efficiency of 3′ end processing in living cells. Using this system in combination with a human genome-wide CRISPR/Cas9 library, we conducted a screen for CPA factors. The screens identified most components of the known core CPA complexes and other known CPA factors. The screens also identified CCNK/CDK12 as a potential core CPA factor, and RPRD1B as a CPA factor that binds RNA and regulates the release of RNA polymerase II at the 3′ ends of genes. Thus, this dual fluorescence reporter coupled with CRISPR/Cas9 screens reliably identifies bona fide CPA factors and provides a platform for investigating the requirements for CPA in various contexts.

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Section: Resultsmentioning

confidence: 99%

Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter

Ni,

Ahmed,

Nabeel-Shah

et al. 2024

Nucleic Acids Research

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show abstract

“…There is, also, a growing interest in the metabolic remodeling of intercellular matrix proteins, including the action of some cathepsins [514,515]. Recently, as an example of an expansive analysis of our biocenosis, it has been found that some viruses may affect/interfere with the fine-tuned system of selection of mRNAs to be translated into newly formed proteins [516]. (h) Excess of energy-providing nutrients.…”

Section: Cell-related Mechanisms: Bi Biochemical Inflammationmentioning

confidence: 99%

The Metabolic Syndrome, a Human Disease

Alemany

2024

IJMS

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This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS’s origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this ‘very’ human disease.

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“…RBPs affect every aspect of RNA biology, including pre‐mRNA splicing, RNA methylation modification, translation, and degeneration of mRNA. RBPs not only modulate each of these biological processes but also establish a link between them 14–16 . Therefore, RBPs play a central role in post‐transcriptional gene regulation (PTGR).…”

Section: Introductionmentioning

confidence: 99%

“…RBPs not only modulate each of these biological processes but also establish a link between them. 14 , 15 , 16 Therefore, RBPs play a central role in post‐transcriptional gene regulation (PTGR). The dynamic interaction between RBPs and their RNA targets is mediated with RNA‐binding domains (RBDs) residing exclusively in RBPs.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles ofRNAbinding proteins in intervertebral disc degeneration and osteoarthritis

Li,

Gao

et al. 2023

Orthopaedic Surgery

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The etiology of intervertebral disc degeneration (IDD) and osteoarthritis (OA) is complex and multifactorial. Both predisposing genes and environmental factors are involved in the pathogenesis of IDD and OA. Moreover, epigenetic modifications affect the development of IDD and OA. Dysregulated phenotypes of nucleus pulposus (NP) cells and OA chondrocytes, including apoptosis, extracellular matrix disruption, inflammation, and angiogenesis, are involved at all developmental stages of IDD and OA. RNA binding proteins (RBPs) have recently been recognized as essential post‐transcriptional regulators of gene expression. RBPs are implicated in many cellular processes, such as proliferation, differentiation, and apoptosis. Recently, several RBPs have been reported to be associated with the pathogenesis of IDD and OA. This review briefly summarizes the current knowledge on the RNA‐regulatory networks controlled by RBPs and their potential roles in the pathogenesis of IDD and OA. These initial findings support the idea that specific modulation of RBPs represents a promising approach for managing IDD and OA.

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Modulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells

Cited by 8 publications

References 71 publications

Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter

Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter

The Metabolic Syndrome, a Human Disease

Emerging roles ofRNAbinding proteins in intervertebral disc degeneration and osteoarthritis

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