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.

Assembly and function of small RNA – Argonaute protein complexes

2014 ◽  
Vol 395 (6) ◽  
pp. 611-629 ◽  
Author(s):  
Anne Dueck ◽  
Gunter Meister
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Small Rna ◽  
Small Rnas ◽  
Atp Hydrolysis ◽  
Protein Complexes ◽  
Protein Family ◽  
Argonaute Protein ◽  
Argonaute Proteins ◽  
And Function

Abstract Small RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi-interacting RNAs (piRNAs) are important regulators of gene expression in various organisms. Small RNAs bind to a member of the Argonaute protein family and are incorporated into larger structures that mediate diverse gene silencing events. The loading of Argonaute proteins with small RNAs is aided by a number of auxiliary factors as well as ATP hydrolysis. This review will focus on the mechanisms of Argonaute loading in different organisms. Furthermore, we highlight the versatile functions of small RNA-Argonaute protein complexes in organisms from all three kingdoms of life.

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 Small RNA molecules in the regulation of spermatogenesis

Reproduction ◽  
2009 ◽  
Vol 137 (6) ◽  
pp. 901-911 ◽  
Author(s):  
Zuping He ◽  
Maria Kokkinaki ◽  
Disha Pant ◽  
G Ian Gallicano ◽  
Martin Dym
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Small Interfering Rnas ◽  
Rna Molecules ◽  
Open Questions ◽  
Complex Process ◽  
Potential Applications ◽  
Pachytene Spermatocytes ◽  
Mitotic Proliferation

Small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs), have recently emerged as important regulators of gene expression at the post-transcriptional or translation level. Significant progress has recently been made utilizing small RNAs in elucidating the molecular mechanisms regulating spermatogenesis. Spermatogenesis is a complex process that involves the division and eventual differentiation of spermatogonial stem cells into mature spermatozoa. The process of spermatogenesis is composed of several phases: mitotic proliferation of spermatogonia to produce spermatocytes; two meiotic divisions of spermatocytes to generate haploid round spermatids; and spermiogenesis, the final phase that involves the maturation of early-round spermatids into elongated mature spermatids. A number of miRNAs are expressed abundantly in male germ cells throughout spermatogenesis, while piRNAs are only present in pachytene spermatocytes and round spermatids. In this review, we first address the synthesis, mechanisms of action, and functions of siRNA, miRNA, and piRNA, and then we focus on the recent advancements in defining the small RNAs in the regulation of spermatogenesis. Concerns pertaining to the use of siRNAs in exploring spermatogenesis mechanisms and open questions in miRNAs and piRNAs in this field are highlighted. The potential applications of small RNAs to male contraception and treatment for male infertility and testicular cancer are also discussed.

scholarly journals Nuage condensates: accelerators or circuit breakers for sRNA silencing pathways?

RNA ◽  
2021 ◽  
pp. rna.079003.121
Author(s):  
John Paul Tsu Ouyang ◽  
Geraldine Seydoux
Keyword(s):  
Germ Cells ◽  
Small Rnas ◽  
Circuit Breakers ◽  
C Elegans ◽  
Silencing Pathways ◽  
And Function

Nuage are RNA-rich condensates that assemble around the nuclei of developing germ cells. Many proteins required for the biogenesis and function of silencing small RNAs (sRNAs) enrich in nuage, and it is often assumed that nuage is the cellular site where sRNAs are synthesized and encounter target transcripts for silencing. Using C. elegans as a model, we examine the complex multi-condensate architecture of nuage and review evidence for compartmentalization of silencing pathways. We consider the possibility that nuage condensates balance the activity of competing sRNA pathways and serve to limit, rather than enhance, sRNA amplification to protect transcripts from dangerous run-away silencing.

scholarly journals Protease-mediated processing of Argonaute proteins controls small RNA association

2020 ◽  
Author(s):  
Rajani Kanth Gudipati ◽  
Kathrin Braun ◽  
Foivos Gypas ◽  
Daniel Hess ◽  
Jan Schreier ◽  
...  
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Proteolytic Processing ◽  
Genome Integrity ◽  
Wild Type ◽  
Selfish Genetic Elements ◽  
Argonaute Proteins ◽  
Processing Activity ◽  
Rna Pathways

SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Desilencing of repeat- and transposon-derived transcripts, DNA damage and acute sterility ensue. These phenotypes are recapitulated when WAGO-1 and WAGO-3 are rendered resistant to DFP-3-mediated processing, identifying them as critical substrates of DPF-3. We conclude that N-terminal processing of Ago proteins regulates their activity and promotes discrimination of self from non-self by ensuring association with the proper complement of small RNAs.Graphical Abstract: The role of DPF-3 in the fertility of the animalsIn wild type animals, the WAGO-1 and WAGO-3 Argonaute proteins are produced as immature pro-proteins with N-termini (N) that are unusually rich in prolines (P). N-terminal processing by DPF-3 is required for loading of the proper small RNA cargo and stabilization of WAGO-3. Accordingly, loss of this processing activity causes desilencing of transposable elements (TE), cell death and sterility.

scholarly journals MiR&moRe2: A Bioinformatics Tool to Characterize microRNAs and microRNA-Offset RNAs from Small RNA-Seq Data

2020 ◽  
Vol 21 (5) ◽  
pp. 1754 ◽  
Author(s):  
Enrico Gaffo ◽  
Michele Bortolomeazzi ◽  
Andrea Bisognin ◽  
Piero Di Battista ◽  
Federica Lovisa ◽  
...  
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Cell Types ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Sequencing Data ◽  
Research Findings ◽  
Human Blood Cell ◽  
And Function ◽  
Comprehensive Study

MicroRNA-offset RNAs (moRNAs) are microRNA-like small RNAs generated by microRNA precursors. To date, little is known about moRNAs and bioinformatics tools to inspect their expression are still missing. We developed miR&moRe2, the first bioinformatics method to consistently characterize microRNAs, moRNAs, and their isoforms from small RNA sequencing data. To illustrate miR&moRe2 discovery power, we applied it to several published datasets. MoRNAs identified by miR&moRe2 were in agreement with previous research findings. Moreover, we observed that moRNAs and new microRNAs predicted by miR&moRe2 were downregulated upon the silencing of the microRNA-biogenesis pathway. Further, in a sizeable dataset of human blood cell populations, tens of novel miRNAs and moRNAs were discovered, some of them with significantly varied expression levels among the cell types. Results demonstrate that miR&moRe2 is a valid tool for a comprehensive study of small RNAs generated from microRNA precursors and could help to investigate their biogenesis and function.

scholarly journals Levels of sdRNAs in cytoplasm and their association with ribosomes are dependent upon stress conditions but independent from snoRNA expression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna M. Mleczko ◽  
Piotr Machtel ◽  
Mateusz Walkowiak ◽  
Anna Wasilewska ◽  
Piotr J. Pietras ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Synthesis ◽  
Small Rna ◽  
Inhibitory Activity ◽  
Small Rnas ◽  
Stress Conditions ◽  
Dependent Manner ◽  
Rna Molecules ◽  
Stress Dependent ◽  
Ribosome Association

AbstractIn recent years, a number of small RNA molecules derived from snoRNAs have been observed. Findings concerning the functions of snoRNA-derived small RNAs (sdRNAs) in cells are limited primarily to their involvement in microRNA pathways. However, similar molecules have been observed in Saccharomyces cerevisiae, which is an organism lacking miRNA machinery. Here we examined the subcellular localization of sdRNAs in yeast. Our findings reveal that both sdRNAs and their precursors, snoRNAs, are present in the cytoplasm at levels dependent upon stress conditions. Moreover, both sdRNAs and snoRNAs may interact with translating ribosomes in a stress-dependent manner. Likely consequential to their ribosome association and protein synthesis suppression features, yeast sdRNAs may exert inhibitory activity on translation. Observed levels of sdRNAs and snoRNAs in the cytoplasm and their apparent presence in the ribosomal fractions suggest independent regulation of these molecules by yet unknown factors.

scholarly journals GTSF-1 is required for the formation of a functional RNA-dependent RNA Polymerase complex in C. elegans

2018 ◽  
Author(s):  
Miguel Vasconcelos Almeida ◽  
Sabrina Dietz ◽  
Stefan Redl ◽  
Emil Karaulanov ◽  
Andrea Hildebrandt ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Gene Silencing ◽  
Small Rna ◽  
Small Rnas ◽  
Zinc Fingers ◽  
Specific Factor ◽  
Rna Dependent Rna Polymerase ◽  
C Elegans ◽  
Argonaute Proteins ◽  
Rna Pathways

AbstractIn every domain of life, Argonaute proteins and their associated small RNAs regulate gene expression. Despite great conservation of Argonaute proteins throughout evolution, many proteins acting in small RNA pathways are not widely conserved. Gametocyte-specific factor 1 (Gtsf1) proteins, characterized by two tandem CHHC zinc fingers and an unstructured, acidic C-terminal tail, are conserved in animals and act in small RNA pathways. In fly and mouse, they are required for fertility and have been shown to interact with Piwi clade Argonautes. We identified T06A10.3 as the Caenorhabditis elegans Gtsf1 homolog and named it gtsf-1. Given its conserved nature and roles in Piwi-mediated gene silencing, we sought out to characterize GTSF-1 in the context of the small RNA pathways of C. elegans. Like its homologs, GTSF-1 is required for normal fertility. Surprisingly, we report that GTSF-1 is not required for Piwi-mediated gene silencing. Instead, gtsf-1 mutants show strong depletion of a class of endogenous small RNAs, known as 26G-RNAs, and fully phenocopy mutants lacking RRF-3, the RNA-dependent RNA Polymerase that synthesizes 26G-RNAs. We show, both in vivo and in vitro, that GTSF-1 specifically and robustly interacts with RRF-3 via its tandem CHHC zinc fingers. Furthermore, we demonstrate that GTSF-1 is required for the assembly of a larger RRF-3 and DCR-1-containing complex, also known as ERIC, thereby allowing for 26G-RNA generation. We propose that GTSF-1 homologs may similarly act to drive the assembly of larger complexes that subsequently act in small RNA production and/or in imposing small RNA-mediated silencing activities.

scholarly journals High-Level Accumulation of Exogenous Small RNAs Not Affecting Endogenous Small RNA Biogenesis and Function in Plants

2014 ◽  
Vol 13 (5) ◽  
pp. 1017-1023
Author(s):  
Wan-xia SHEN ◽  
Neil A Smith ◽  
Chang-yong ZHOU ◽  
Ming-bo WANG
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Rna Biogenesis ◽  
High Level ◽  
And Function

scholarly journals Argonaute Proteins Take Center Stage in Cancers

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 788
Author(s):  
Iwona Nowak ◽  
Aishe A. Sarshad
Keyword(s):  
Cancer Cells ◽  
Small Rna ◽  
Therapeutic Approaches ◽  
Rna Molecules ◽  
Center Stage ◽  
Current State ◽  
Argonaute Proteins ◽  
Tumor Types ◽  
Novel Therapeutic

Argonaute proteins (AGOs) play crucial roles in RNA-induced silencing complex (RISC) formation and activity. AGOs loaded with small RNA molecules (miRNA or siRNA) either catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and target destabilization. miRNAs are well characterized and broadly studied in tumorigenesis; nevertheless, the functions of the AGOs in cancers have lagged behind. Here, we discuss the current state of knowledge on the role of AGOs in tumorigenesis, highlighting canonical and non-canonical functions of AGOs in cancer cells, as well as the biomarker potential of AGO expression in different of tumor types. Furthermore, we point to the possible application of the AGOs in development of novel therapeutic approaches.

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