Specialization and evolution of endogenous small RNA pathways

ABSTRACTEmbryonic axis patterning in Drosophila melanogaster is partly achieved by mRNAs that are maternally localized to the oocyte; the spatio-temporal regulation of these transcripts’ stability and translation is a characteristic feature of oogenesis. While protein regulatory factors are necessary for the translational regulation of some maternal transcripts (e.g. oskar and gurken), small RNA pathways are also known to regulate mRNA stability and translation in eukaryotes. MicroRNAs (miRNAs) are small RNA regulators of gene expression, widely conserved throughout eukaryotic genomes and essential for animal development. The main D. melanogaster anterior determinant, bicoid, is maternally transcribed, but it is not translated until early embryogenesis. We investigated the possibility that its translational repression during oogenesis is mediated by miRNA activity. We found that the bicoid 3’UTR contains a highly conserved, predicted binding site for miR-305. Our studies reveal that miR-305 regulates the translation of a reporter gene containing the bicoid 3’UTR in cell culture, and that miR-305 only partially contributes to bicoid mRNA translational repression during oogenesis. We also found that Processing bodies (P-bodies) in the egg chamber may play a role in stabilizing bicoid and other maternal transcripts. Here, we offer insights into the possible role of P-bodies and the miRNA pathway in the translational repression of bicoid mRNA during oogenesis.

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

Nucleic Acids Research ◽

10.1093/nar/gkaa002 ◽

2020 ◽

Vol 48 (4) ◽

pp. 2050-2072 ◽

Cited By ~ 4

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.

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Meiotic drive mechanisms: lessons from Drosophila

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.1430 ◽

2019 ◽

Vol 286 (1913) ◽

pp. 20191430 ◽

Cited By ~ 8

Author(s):

Cécile Courret ◽

Ching-Ho Chang ◽

Kevin H.-C. Wei ◽

Catherine Montchamp-Moreau ◽

Amanda M. Larracuente

Keyword(s):

Small Rna ◽

Molecular Mechanisms ◽

Meiotic Drive ◽

Gene Duplications ◽

Arms Races ◽

Transport Pathways ◽

Selfish Genetic Elements ◽

Genetic Origins ◽

Drive Systems ◽

Rna Pathways

Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in the Drosophila genus. Recent studies in Drosophila have provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers in Drosophila species. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work in Drosophila has made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.

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Ancient and Novel Small RNA Pathways Compensate for the Loss of piRNAs in Multiple Independent Nematode Lineages

PLoS Biology ◽

10.1371/journal.pbio.1002061 ◽

2015 ◽

Vol 13 (2) ◽

pp. e1002061 ◽

Cited By ~ 77

Author(s):

Peter Sarkies ◽

Murray E. Selkirk ◽

John T. Jones ◽

Vivian Blok ◽

Thomas Boothby ◽

...

Keyword(s):

Small Rna ◽

Rna Pathways

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Bugs Are Not to Be Silenced: Small RNA Pathways and Antiviral Responses in Insects

Annual Review of Virology ◽

10.1146/annurev-virology-110615-042447 ◽

2016 ◽

Vol 3 (1) ◽

pp. 573-589 ◽

Cited By ~ 25

Author(s):

Vanesa Mongelli ◽

Maria-Carla Saleh

Keyword(s):

Small Rna ◽

Antiviral Responses ◽

Rna Pathways

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The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans

Molecular Cell ◽

10.1016/j.molcel.2020.12.004 ◽

2020 ◽

Author(s):

Daniel A. Chaves ◽

Hui Dai ◽

Lichao Li ◽

James J. Moresco ◽

Myung Eun Oh ◽

...

Keyword(s):

Small Rna ◽

C Elegans ◽

Rna Pathways

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Tudor Nuclease Genes and Programmed DNA Rearrangements in Tetrahymena thermophila

Eukaryotic Cell ◽

10.1128/ec.00192-07 ◽

2007 ◽

Vol 6 (10) ◽

pp. 1795-1804 ◽

Cited By ~ 15

Author(s):

Rachel A. Howard-Till ◽

Meng-Chao Yao

Keyword(s):

Sexual Reproduction ◽

Small Rna ◽

Tetrahymena Thermophila ◽

Minor Role ◽

Dna Deletion ◽

Genome Defense ◽

Rna Pathways ◽

A Minor

ABSTRACT Proteins containing a Tudor domain and domains homologous to staphylococcal nucleases are found in a number of eukaryotes. These “Tudor nucleases” have been found to be associated with the RNA-induced silencing complex (A. A. Caudy, R. F. Ketting, S. M. Hammond, A. M. Denli, A. M. Bathoorn, B. B. Tops, J. M. Silva, M. M. Myers, G. J. Hannon, and R. H. Plasterk, Nature 425:411-414, 2003). We have identified two Tudor nuclease gene homologs, TTN1 and TTN2, in the ciliate Tetrahymena thermophila, which has two distinct small-RNA pathways. Characterization of single and double KOs of TTN1 and TTN2 shows that neither of these genes is essential for growth or sexual reproduction. Progeny of TTN2 KOs and double knockouts occasionally show minor defects in the small-RNA-guided process of DNA deletion but appear to be normal in hairpin RNA-induced gene silencing, suggesting that Tudor nucleases play only a minor role in RNA interference in Tetrahymena. Previous studies of Tetrahymena have shown that inserted copies of the neo gene from Escherichia coli are often deleted from the developing macronucleus during sexual reproduction (Y. Liu, X. Song, M. A. Gorovsky, and K. M. Karrer, Eukaryot. Cell 4:421-431, 2005; M. C. Yao, P. Fuller, and X. Xi, Science 300:1581-1584, 2003). This transgene deletion phenomenon is hypothesized to be a form of genome defense. Analysis of the Tudor nuclease mutants revealed exceptionally high rates of deletion of the neo transgene at the TTN2 locus but no deletion at the TTN1 locus. When present in the same genome, however, the neo gene is deleted at high rates even at the TTN1 locus, further supporting a role for trans-acting RNA in this process. This deletion is not affected by the presence of the same sequence in the macronucleus, thus providing a counterargument for the role of the macronuclear genome in specifying all sequences for deletion.

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