Communicating Across Kingdoms?

Researchers pinpoint microRNAs that could play a role in how Wolbachia bacteria manipulate their arthropod hosts.

By | December 15, 2014

Transmission electron micrograph of Wolbachia within an insect cellPLOS BIOLOGY, SCOTT O'NEILLWolbachia bacteria live inside the cells of other species and can strongly influence the lives of their hosts. These bacteria manipulate host reproductive biology to increase their own transmission. Wolbachia have been documented in more than 40 percent of terrestrial arthropods.

Exactly how Wolbachia manage to manipulate a wide variety of hosts has puzzled scientists for decades. In a paper published in PNAS today (December 15), Sassan Asgari from the University of Queensland, Australia, and his colleagues propose a microRNA-mediated mechanism by which Wolbachia could achieve such “cross-kingdom communication.”

“This is one of the first instances showing how the bacteria are communicating with the host at a cellular level,” said Rhitoban Raychoudhury, an evolutionary geneticist at the Indian Institute of Science Education & Research Mohali who was not involved in the work.

Previous studies have shown that Wolbachia can regulate certain microRNAs (miRNAs) in the host Aedes aegypti, resulting in increased production of certain enzymes and decreased production of others, both in favor Wolbachia persistence.  Using deep sequencing, Asgari’s team found that two miRNAs, WsnRNA-46 and WsnRNA-49, were highly expressed in Wolbachia-infected mosquitoes—and especially in cells where the bacteria dwelled. WsnRNA-46 and WsnRNA-49 are both about 30 nucleotides long, have stem-loop structures, and are far from each other on the genome, governed by independent promoters.

So the team sought to evaluate whether other host species expressed these miRNAs. The researchers infected two strains of Drosophila, D. melanogaster and D. simulans, with two different Wolbachia strains. The infection pattern in Drosophila was similar to mosquitoes infected with Wolbachia: both miRNAs turned up in males and females, and were not expressed in non-infected cells. The group then conducted a sequence homology search among available Wolbachia sequences, finding that precursors to both miRNAs were conserved in most strains belonging to Wolbachia supergroup A.   

“It is highly likely that other strains of Wolbachia produce miRNAs, but whether they are involved in the same function requires further investigation,” Asgari told The Scientist.

A simple Northern Blot revealed that the miRNAs were localized to tissues where mosquitoes are known to harbor Wolbachia, such as in the ovaries. The group then studied how the miRNAs interacted with the Wolbachia genome. Beginning with a list of candidate genes, the researchers homed in on the gene that codes for the enzyme UDP-N-acetylmuramoyalanine-D-glutamate ligase (murD), which had maximum sequence complementarity to WsnRNA-46 and WsnRNA-49. The researchers then used cloning to show that murD was in fact targeted by the Wolbachia miRNAs, resulting in a down-regulation of murD.

Might these miRNAs influence host gene expression? A bioinformatics screen turned up target genes in the A. aegypti genome that showed special complementarity with a part of the protein dynein. To ensure their own replication, Wolbachia have been shown to use the microtubule machinery of the host, in which dynein plays a critical role.

But Bryan Cullen, a molecular geneticist at Duke University, is skeptical of the role of Wolbachia miRNAs in host gene regulation. “This argument that miRNAs increase target gene expression—not repress—has no precedent,” he told The Scientist in an e-mail.

“The study is very intriguing, and opens up new mechanisms by which Wolbachia and other bacteria could manipulate or more generally interact with their hosts,” said evolutionary geneticist John Werren from the University of Rochester in New York. “I am not sure that I would call this ‘communication,’ however,” he added, as the authors have in their paper.

How Wolbachia interact with their various hosts remains a mystery. And miRNAs may be but one piece of this puzzle, the authors noted.

“Surely, this mechanism shown by the authors is a tantalizing glimpse on how Wolbachia gets about controlling host gene expression,” said Raychoudhury.

J. Mayoral et al., “Wolbachia small noncoding RNAs and their role in cross-kingdom communications,” PNAS, doi:10.1073/pnas.1420131112, 2014.

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Avatar of: James V. Kohl

James V. Kohl

Posts: 481

December 16, 2014

“I am not sure that I would call this ‘communication,’ however,” he added, as the authors have in their paper.

I'm rather certain that no evolutionary theorist will recognize this as communication because they typically claim mutations can be linked to increasing organismal complexity. This work indirectly links mutations to perturbed protein folding, diseases, and disorders.

Works published by Leslie Vosshall's group and by others have linked the epigenetic landscape to the physical landscape of DNA in the organized genomes of insects via experience-dependent  de novo creation of olfactory receptors. Their works link the epigenetically-effected microRNA/messenger RNA balance from RNA-directed DNA methylation and RNA-mediated amino acid substitutions to cell type differentiation via conserved molecular mechanisms in species from microbes to man.

The molecular mechanisms are nutrient-dependent and pheromone-controlled because the nutrient-dependent amino acid substitutions must be fixed in organized genomes via protein folding in the context of the species-specific physiology of reproduction. That fact links Darwin's 'conditions of life' to cell type differentiation via examples provided in Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

For supporting documentation that places the role of mutations in their proper perspective of pseudoscientific nonsense that began with de Vries definition of "mutation," see: Amino Acid Residues Contributing to Function of the Heteromeric Insect Olfactory Receptor Complex ; orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET; and Evolution of mosquito preference for humans linked to an odorant receptor.

Those who accept definitions and try to link them to biologically-based behavior have done so without recognizing the role that feedback loops must play  in protein folding that links ecological variation to ecological adaptations. Instead, they claim mutations lead to the evolution of biodiversity, when serious scientists know that Feedback loops link odor and pheromone signaling with reproduction in species from microbes to man via conserved molecular mechanisms of communication. See also: Signaling Crosstalk: Integrating Nutrient Availability and Sex. Let's stop the nonsense and call communication what it is, and recognize it for what it does.

Communication enables nutrient-dependent pheromone-controlled cell type differentiation via amino acid substitutions that control thermodynamic cycles of protein biosynthesis and degradation. Mutations perturb protein folding, which is why they are not beneficial and cannot lead to the evolution of increasing organismal complexity.

Avatar of: Rakesh YashRoy

Rakesh YashRoy

Posts: 2

December 18, 2014

Inter-species communication between microbes and their host or target cells is routinely mediated via membrane vesicle trafficking as nanovesicles carrying variety of microbial signal molecules for variety of tasks and puposes in order to rule the environment. For more detail, see http://www.labome.org/research/Membrane-vesicle-trafficking-in-prokaryotes-molecular-biomechanics-of-bio...

Avatar of: Sassan Asgari

Sassan Asgari

Posts: 1

January 22, 2015

“This argument that miRNAs increase target gene expression—not repress—has no precedent,” he told The Scientist in an e-mail.

This comment is quite surprising as there are several papers showing that miRNAs may increase the transcript levels of their targets, by inducing transcription (1)and translation (2), repressing nonsense-mediated RNA decay (3)or increasing mRNA stability (4). These are only some of the examples (see also a review by 5). The classical example is miR-122 that enhances hepatitis C virus replication by interacting with its target sequences in the 5’UTR of the virus (6). This interaction leads to enhanced RNA stability and translation stimulation (1).

References:

1.         Conrad K, et al. (2013) MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation. PLoS ONE 8:e56272.

2.         Orom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5' UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460-471.

3.         Bruno IG, et al. (2011) Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay. Mol Cell 42:500-510.

4.         Ma F, et al. (2010) MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation J Immunol 184:6053-6059.

5.         Vasudevan S (2012) Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA 3:311-330.

6.         Henke JI, et al. (2008) microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 27:3300-3310.

 

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