scholarly journals tRNA 2′-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila

2020 ◽  
Vol 48 (4) ◽  
pp. 2050-2072 ◽  
Author(s):  
Margarita T Angelova ◽  
Dilyana G Dimitrova ◽  
Bruno Da Silva ◽  
Virginie Marchand ◽  
Caroline Jacquier ◽  
...  
Keyword(s):  
Small Rna ◽  
Rna Structure ◽  
Rna Silencing ◽  
Defense Mechanisms ◽  
Rna Virus ◽  
Virus Infections ◽  
Self Recognition ◽  
Silencing Pathways ◽  
Rna Pathways ◽  
And Function

Abstract 2′-O-Methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNAPhe, tRNATrp and tRNALeu, while CG5220 methylates position C32 in the same tRNAs and also targets additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as lifespan reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalyzing Nm at specific tRNAs and small RNA-induced gene silencing pathways.

scholarly journals tRNA 2’-O-methylation modulates small RNA silencing and life span in Drosophila

2019 ◽  
Author(s):  
Margarita T. Angelova ◽  
Dilyana G. Dimitrova ◽  
Bruno Da Silva ◽  
Virginie Marchand ◽  
Catherine Goyenvalle ◽  
...  
Keyword(s):  
Life Span ◽  
Small Rna ◽  
Rna Structure ◽  
Rna Silencing ◽  
Defense Mechanisms ◽  
Rna Virus ◽  
Virus Infections ◽  
Self Recognition ◽  
Rna Pathways ◽  
And Function

Abstract2’-O-methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two novel Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1, respectively. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNAPhe, tRNATrp and tRNALeu, while subsequently, CG5220 methylates position C32 in the same tRNAs and targets also additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as life span reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalysing Nm at specific tRNAs and small RNA-induced gene silencing pathways.

scholarly journals Viral Suppressors of RNA Silencing Hinder Exogenous and Endogenous Small RNA Pathways in Drosophila

PLoS ONE ◽  
2009 ◽  
Vol 4 (6) ◽  
pp. e5866 ◽  
Author(s):  
Bassam Berry ◽  
Safia Deddouche ◽  
Doris Kirschner ◽  
Jean-Luc Imler ◽  
Christophe Antoniewski
Keyword(s):  
Small Rna ◽  
Rna Silencing ◽  
Rna Pathways ◽  
Viral Suppressors

scholarly journals Formation and Function of Liquid-Like Viral Factories in Negative-Sense Single-Stranded RNA Virus Infections

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 126
Author(s):  
Justin M. Su ◽  
Maxwell Z. Wilson ◽  
Charles E. Samuel ◽  
Dzwokai Ma
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Host Responses ◽  
Future Research ◽  
Virus Infections ◽  
Infected Cells ◽  
And Function ◽  
Negative Sense ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the cytoplasm of infected cells. These studies further reveal the structural and functional complexity of viral IB factories and provide a foundation for their future research. Herein, we review the literature leading to the discovery of LLPS-driven formation of IBs in NNS RNA virus-infected cells and the identification of viral scaffold components involved, and then outline important questions and challenges for IB assembly and disassembly. We discuss the functional implications of LLPS in the life cycle of NNS RNA viruses and host responses to infection. Finally, we speculate on the potential mechanisms underlying IB maturation, a phenomenon relevant to many human diseases.

Small RNA Silencing Pathways

2007 ◽  
pp. 75-88
Author(s):  
Phillip Zamore ◽  
Alla Sigova
Keyword(s):  
Small Rna ◽  
Rna Silencing ◽  
Silencing Pathways

scholarly journals New Perspectives on the Biogenesis of Viral Inclusion Bodies in Negative-Sense RNA Virus Infections

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1460
Author(s):  
Olga Dolnik ◽  
Gesche K. Gerresheim ◽  
Nadine Biedenkopf
Keyword(s):  
Inclusion Bodies ◽  
Rna Binding ◽  
Rna Virus ◽  
Virus Infections ◽  
Binding Domains ◽  
Protein Functions ◽  
Viral Inclusion ◽  
Dynamic Structures ◽  
And Function ◽  
Nucleoprotein N

Infections by negative strand RNA viruses (NSVs) induce the formation of viral inclusion bodies (IBs) in the host cell that segregate viral as well as cellular proteins to enable efficient viral replication. The induction of those membrane-less viral compartments leads inevitably to structural remodeling of the cellular architecture. Recent studies suggested that viral IBs have properties of biomolecular condensates (or liquid organelles), as have previously been shown for other membrane-less cellular compartments like stress granules or P-bodies. Biomolecular condensates are highly dynamic structures formed by liquid-liquid phase separation (LLPS). Key drivers for LLPS in cells are multivalent protein:protein and protein:RNA interactions leading to specialized areas in the cell that recruit molecules with similar properties, while other non-similar molecules are excluded. These typical features of cellular biomolecular condensates are also a common characteristic in the biogenesis of viral inclusion bodies. Viral IBs are predominantly induced by the expression of the viral nucleoprotein (N, NP) and phosphoprotein (P); both are characterized by a special protein architecture containing multiple disordered regions and RNA-binding domains that contribute to different protein functions. P keeps N soluble after expression to allow a concerted binding of N to the viral RNA. This results in the encapsidation of the viral genome by N, while P acts additionally as a cofactor for the viral polymerase, enabling viral transcription and replication. Here, we will review the formation and function of those viral inclusion bodies upon infection with NSVs with respect to their nature as biomolecular condensates.

scholarly journals From transcription to translation: new insights in the structure and function of Argonaute protein

2012 ◽  
Vol 3 (6) ◽  
pp. 545-559
Author(s):  
Corinna Giorgi ◽  
Carlo Cogoni ◽  
Caterina Catalanotto
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Biological Function ◽  
Rna Molecules ◽  
Argonaute Proteins ◽  
Ancestral Function ◽  
Higher Eukaryotes ◽  
Silencing Pathways ◽  
Genome Protection ◽  
And Function

AbstractArgonaute proteins play a central role in gene silencing pathways mediated by small RNA molecules. The ancestral function of small RNA-dependent silencing is related to genome protection against parasitic nucleic acids, such as transposons and viruses. However, new classes of small RNAs are continuously being uncovered in all higher eukaryotes in which they play important functions in processes ranging from embryonic development to differentiation to cell proliferation and metabolism. Small RNAs have variegated biogenesis pathways and accomplish distinct functions. Nevertheless, it appears that all small RNAs work merely as guides in recognizing the target RNAs invariably relying on the interaction with Argonaute proteins and associated factors for their biological function. Here, we discuss recent findings on the structure and regulation of mammalian Argonaute proteins and overview the various roles that these versatile proteins play in regulating gene expression.

scholarly journals Distinctive profiles of small RNA couple inverted repeat-induced post-transcriptional gene silencing with endogenous RNA silencing pathways inArabidopsis

RNA ◽  
2014 ◽  
Vol 20 (12) ◽  
pp. 1987-1999 ◽  
Author(s):  
Tadeusz Wroblewski ◽  
Marta Matvienko ◽  
Urszula Piskurewicz ◽  
Huaqin Xu ◽  
Belinda Martineau ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Small Rna ◽  
Inverted Repeat ◽  
Rna Silencing ◽  
Transcriptional Gene Silencing ◽  
Post Transcriptional Gene Silencing ◽  
Silencing Pathways
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