Emergent RNA-RNA interactions can promote stability in a nascent phototrophic endosymbiosis
Preprint posted on 13 May 2021 https://www.biorxiv.org/content/10.1101/2021.04.11.439338v2
Article now published in Proceedings of the National Academy of Sciences at http://dx.doi.org/10.1073/pnas.2108874118
Unexpected host-endosymbiont RNA-RNA interactions discourage Paramecium from digesting its symbiotic partners.
Selected by Olivia TidswellCategories: cell biology, ecology, evolutionary biology, microbiology, molecular biology
Background
Endosymbiosis has played a fundamental role in eukaryote evolution, giving rise to vitally important organelles such as mitochondria and chloroplasts. However, the interests of a host cell and its endosymbionts do not always align, and these relationships are frequently fraught with conflict. What is stopping a host cell from simply digesting its tenants for a quick meal in a pinch?
In this preprint, Jenkins and colleagues investigate this question in the context of a eukaryotic-eukaryotic endosymbiosis, specifically the nascent endosymbiosis between the ciliate protist Paramecium bursaria and the single-celled algae Chlorella. A single Paramecium may contain hundreds of Chlorella cells, housed inside modified phagosomes. Here, Chlorella can evade potential predators and utilise metabolic products from its host (such as amino acids and CO2). In return, Chlorella provides its host with the products of photosynthesis. This symbiosis is still relatively new, and both partners are able to survive independently of each other.
There is no doubt that P. bursaria wields much of the power in this arrangement. At any time, it could unleash digestive lysosomes to break down its endosymbionts and recycle all of that valuable biomatter. Here, Jenkins and colleagues describe an emergent mechanism that punishes this kind of over-exploitation, and therefore promotes co-operation between host and endosymbiont.
Key findings
Induction of endosymbiont digestion reduces the growth of P. bursaria
One of the benefits of the P. bursaria–Chlorella symbiosis as a study system is that it can be readily manipulated using the protein synthesis inhibitor cycloheximide. This chemical conveniently switches off protein synthesis in Chlorella, but not Paramecium, cells, which induces P. bursaria to digest its endosymbionts (see Kodama and Fujishima, 2008 for more information). The authors show that extended cycloheximide exposure dramatically reduces the growth of symbiotic P. bursaria cultures, an effect that is not observed in the non-symbiotic species P. tetraurelia. These observations suggest that digestion of Chlorella (not exposure to cycloheximide) limits the growth of P. bursaria.
Figure 1C from the preprint. Cycloheximide exposure reduces culture growth of P. bursaria, but not of non-symbiotic P. tetraurelia.
Reduced growth of P. bursaria after endosymbiont digestion is dependent on endogenous RNAi machinery
One possible explanation for this reduction in growth is that destroying its endosymbionts renders P. bursaria unable to benefit from photosynthesis, effectively exchanging a valuable ongoing source of sustenance for a temporary feast. However, the authors show that this is unlikely to be the primary downside to Chlorella digestion. Reduced growth of P. bursaria after cycloheximide treatment can be almost completely rescued by knocking down RNA interference (RNAi) machinery, such as Dicer (Dcr1), PiwiA1 andPds1. This suggests that the reduction in growth rate observed after Chlorella digestion is dependent on the endogenous RNAi pathway of Paramecium.
Figure 1D from the preprint. Knockdown of Dicer1, a mediator of the RNAi pathway, can partially rescue growth inhibition after cycloheximide exposure compared to controls.
Endosymbiont digestion results in Dicer-dependent accumulation of short, endosymbiont-derived RNAs
The authors propose that digested Chlorella cells release RNAs that are processed into short RNAs (sRNAs) by the host’s Dicer pathway, and that these sRNAs are ultimately responsible for the effects on host fitness. In agreement with this hypothesis, they find that cycloheximide exposure increases the abundance of endosymbiont-derived sRNAs in P. bursaria cells. sRNA abundance is reduced if host Dicer is knocked down by RNAi. This suggests that host Dicer is able to process RNA released from digested Chlorella cells into sRNAs. Furthermore, the authors find that many of these endosymbiont-derived sRNAs have homology to host mRNA transcripts, and therefore could potentially interact with them.
Endosymbiont-derived sRNA sequences can be used by host RNAi machinery to downregulate the expression of homologous host genes
The authors investigated whether endosymbiont-derived sRNAs can interact with host mRNA using an elegant series of experiments. Firstly, they chose ten sRNAs with high homology to host mRNA transcripts, cloned them into a plasmid, and delivered the plasmid into P. bursaria cells by allowing them to feed on transformed E. coli. Exposure to this chimeric plasmid retarded the growth of P. bursaria cultures in a Dicer-dependent manner. Next, the authors narrowed down the cause of this retardation to three of the ten endosymbiont-derived sRNAs, with homology to host elongation factor 1α, heat shock protein 90 and tubulin-ß mRNAs. The expression of at least two of these genes was reduced in P. bursaria cells exposed to the chimeric plasmid, and could be rescued by knockdown of Dicer. Together, these experiments suggest that sRNAs derived from digested Chlorella cells can be utilized by the host’s endogenous RNAi pathway to knock down homologous host genes, and to reduce host fitness.
Figures 3B and E from the preprint. B| P. bursaria culture growth is inhibited after exposure to a vector encoding ten different endosymbiont-derived sRNAs (“chimera”). This effect can be partially rescued by simultaneous knockdown of Dicer1. E| Exposure of P. bursaria to the chimeric vector described in B results in the downregulation of homologous host transcripts.
Why is this work important, and what did I like about it?
This work characterizes a novel phenomenon that punishes host cells for overexploitation of their endosymbionts – namely, RNAi-mediated interactions between endosymbiont-derived short RNAs and host mRNAs, which the authors describe as “RNA collisions”. Importantly, RNA collisions do not rely on a long history of co-evolution between host and endosymbiont, and could act to enforce co-operation even in nascent endosymbioses. This phenomenon is therefore a promising explanation for how endosymbioses might be stabilised before more specific dependencies or manipulations evolve.
I chose to highlight this preprint not just because I think that the results are surprising and exciting, but also because I appreciated how clearly and openly the authors discussed the strengths and limitations of their experiments. They go to great lengths to test alternative explanations for their observations, and to justify and caveat their experimental approaches, making their eventual conclusions all the more convincing. I am excited to see how future work tests the broader relevance of RNA collisions in stabilizing emergent endosymbioses.
Additional references:
Kodama, Y. and Fujishima, M. (2008). Cycloheximide Induces Synchronous Swelling of Perialgal Vacuoles Enclosing Symbiotic Chlorella vulgaris and Digestion of the Algae in the Ciliate Paramecium bursaria. Protist 159, 483–494.
Posted on: 17 May 2021
doi: https://doi.org/10.1242/prelights.28985
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
TLR2 Regulates Hair Follicle Cycle and Regeneration via BMP Signaling
Mechano-dependent sorbitol accumulation supports biomolecular condensate
CRISPR-dependent base editing screens identify separation of function mutants of RADX with altered RAD51 regulatory activity
Also in the ecology category:
Hypoxia blunts angiogenic signaling and upregulates the antioxidant system in elephant seal endothelial cells
Laboratory evolution of flies to morphogen dosage via rapid maternal changes reveals predictable outcomes
Mapping current and future thermal limits to suitability for malaria transmission by the invasive mosquito Anopheles stephensi
Also in the evolutionary biology category:
The genome of the colonial hydroid Hydractinia reveals their stem cells utilize a toolkit of evolutionarily shared genes with all animals
A transposase-derived gene required for human brain development
Interspecies blastocyst complementation generates functional rat cell-derived forebrain tissues in mice
Also in the microbiology category:
Glycan-specific IgM is critical for human immunity to Staphylococcus aureus
Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy
Coxiella burnetii actively blocks IL-17-induced oxidative stress in macrophages
Also in the molecular biology category:
Hypoxia blunts angiogenic signaling and upregulates the antioxidant system in elephant seal endothelial cells
A Phosphoproteomics Data Resource for Systems-level Modeling of Kinase Signaling Networks
PYCR1 Levels Track with Premature and Chronological Skin Aging
preListscell biology category:
in theThe Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
List by | Dey Lab, Amanda Haage |
Also in the ecology category:
EMBO | EMBL Symposium: The organism and its environment
This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).
List by | Girish Kale |
Bats
A list of preprints dealing with the ecology, evolution and behavior of bats
List by | Baheerathan Murugavel |
Also in the evolutionary biology category:
EMBO | EMBL Symposium: The organism and its environment
This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).
List by | Girish Kale |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
COVID-19 / SARS-CoV-2 preprints
List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic
List by | Dey Lab, Zhang-He Goh |
1
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
List by | Alexa Sadier |
Also in the microbiology category:
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
List by | Dey Lab, Samantha Seah |
1
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
List by | Zhang-He Goh |
Also in the molecular biology category:
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar et al. |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
List by | Sandra Franco Iborra |