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Publications (10 of 20) Show all publications
Kärblane, K., Gerassimenko, J., Nigul, L., Piirsoo, A., Smialowska, A., Vinkel, K., . . . Sarmiento, C. (2015). ABCE1 Is a Highly Conserved RNA Silencing Suppressor. PLoS ONE, 10(2), Article ID e0116702.
Open this publication in new window or tab >>ABCE1 Is a Highly Conserved RNA Silencing Suppressor
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0116702Article in journal (Refereed) Published
Abstract [en]

ATP-binding cassette sub-family E member 1 (ABCE1) is a highly conserved protein among eukaryotes and archaea. Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea. Here we report another conserved function of ABCE1. We have previously described AtRLI2, the homolog of ABCE1 in the plant Arabidopsis thaliana, as an endogenous suppressor of RNA silencing. In this study we show that this function is conserved: human ABCE1 is able to suppress RNA silencing in Nicotiana benthamiana plants, in mammalian HEK293 cells and in the worm Caenorhabditis elegans. Using co-immunoprecipitation and mass spectrometry, we found a number of potential ABCE1-interacting proteins that might support its function as an endogenous suppressor of RNA interference. The interactor candidates are associated with epigenetic regulation, transcription, RNA processing and mRNA surveillance. In addition, one of the identified proteins is translin, which together with its binding partner TRAX supports RNA interference.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-26400 (URN)10.1371/journal.pone.0116702 (DOI)000349444900060 ()25659154 (PubMedID)2-s2.0-84922720162 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies, 300501
Available from: 2015-02-12 Created: 2015-02-12 Last updated: 2018-07-18Bibliographically approved
Smialowska, A., Djupedal, I., Wang, J., Kylsten, P., Swoboda, P. & Ekwall, K. (2014). RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe. Biochemical and Biophysical Research Communications - BBRC, 444(2), 254-259
Open this publication in new window or tab >>RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe
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2014 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 444, no 2, p. 254-259Article in journal (Other academic) Published
Abstract [en]

RNA interference (RNAi) is a gene silencing mechanism conserved from fungi to mammals. Small interfering RNAs are products and mediators of the RNAi pathway and act as specificity factors in recruiting effector complexes. The Schizosaccharomyces pombe genome encodes one of each of the core RNAi proteins, Dicer, Argonaute and RNA-dependent RNA polymerase (dcr1, ago1, rdp1). Even though the function of RNAi in heterochromatin assembly in S. pombe is established, its role in controlling gene expression is elusive. Here, we report the identification of small RNAs mapped anti-sense to protein coding genes in fission yeast. We demonstrate that these genes are up-regulated at the protein level in RNAi mutants, while their mRNA levels are not significantly changed. We show that the repression by RNAi is not a result of heterochromatin formation. Thus, we conclude that RNAi is involved in post-transcriptional gene silencing in S. pombe.

Keywords
Fission yeast, PTGS, RNAi
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-22232 (URN)10.1016/j.bbrc.2014.01.057 (DOI)000331923500025 ()24462781 (PubMedID)2-s2.0-84892926000 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies, 300501Swedish Cancer Society, CAN-2009Swedish Research Council, VR-NT-2007-4722
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2018-07-20Bibliographically approved
Rhind, N., Chen, Z., Yassour, M., Thompson, D. A., Haas, B. J., Habib, N., . . . Nusbaum, C. (2011). Comparative Functional Genomics of the Fission Yeasts. Science, 332(6032), 930-936
Open this publication in new window or tab >>Comparative Functional Genomics of the Fission Yeasts
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2011 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 332, no 6032, p. 930-936Article in journal (Refereed) Published
Abstract [en]

The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.

National Category
Biochemistry and Molecular Biology Microbiology
Identifiers
urn:nbn:se:sh:diva-14957 (URN)10.1126/science.1203357 (DOI)000290766600034 ()21511999 (PubMedID)2-s2.0-79956319465 (Scopus ID)
Available from: 2012-01-24 Created: 2012-01-24 Last updated: 2018-07-18Bibliographically approved
Massinen, S., Hokkanen, M.-E., Matsson, H., Tammimies, K., Tapia-Paez, I., Dahlstrom-Heuser, V., . . . Kere, J. (2011). Increased Expression of the Dyslexia Candidate Gene DCDC2 Affects Length and Signaling of Primary Cilia in Neurons. PLoS ONE, 6(6), e20580
Open this publication in new window or tab >>Increased Expression of the Dyslexia Candidate Gene DCDC2 Affects Length and Signaling of Primary Cilia in Neurons
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2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e20580-Article in journal (Refereed) Published
Abstract [en]

DCDC2 is one of the candidate susceptibility genes for dyslexia. It belongs to the superfamily of doublecortin domain containing proteins that bind to microtubules, and it has been shown to be involved in neuronal migration. We show that the Dcdc2 protein localizes to the primary cilium in primary rat hippocampal neurons and that it can be found within close proximity to the ciliary kinesin-2 subunit Kif3a. Overexpression of DCDC2 increases ciliary length and activates Shh signaling, whereas downregulation of Dcdc2 expression enhances Wnt signaling, consistent with a functional role in ciliary signaling. Moreover, DCDC2 overexpression in C. elegans causes an abnormal neuronal phenotype that can only be seen in ciliated neurons. Together our results suggest a potential role for DCDC2 in the structure and function of primary cilia.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-14951 (URN)10.1371/journal.pone.0020580 (DOI)000291734100009 ()21698230 (PubMedID)2-s2.0-79959242358 (Scopus ID)
Available from: 2012-01-24 Created: 2012-01-24 Last updated: 2018-07-18Bibliographically approved
Stenvall, J., Fierro-Gonzalez, J. C., Swoboda, P., Saamarthy, K., Cheng, Q., Cacho-Valadez, B., . . . Tuck, S. (2011). Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 108(3), 1064-1069
Open this publication in new window or tab >>Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans
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2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 3, p. 1064-1069Article in journal (Refereed) Published
Abstract [en]

Selenoproteins, in particular thioredoxin reductase, have been implicated in countering oxidative damage occurring during aging but the molecular functions of these proteins have not been extensively investigated in different animal models. Here we demonstrate that TRXR-1 thioredoxin reductase, the sole selenoprotein in Caenorhabditis elegans, does not protect against acute oxidative stress but functions instead together with GSR-1 glutathione reductase to promote the removal of old cuticle during molting. We show that the oxidation state of disulfide groups in the cuticle is tightly regulated during the molting cycle, and that when trxr-1 and gsr-1 function is reduced, disulfide groups in the cuticle remain oxidized. A selenocysteine-to-cysteine TRXR-1 mutant fails to rescue molting defects. Furthermore, worms lacking SELB-1, the C. elegans homolog of Escherichia coli SelB or mammalian EFsec, a translation elongation factor known to be specific for selenocysteine in E. coli, fail to incorporate selenocysteine, and display the same phenotype as those lacking trxr-1. Thus, TRXR-1 function in the reduction of old cuticle is strictly selenocysteine dependent in the nematode. Exogenously supplied reduced glutathione reduces disulfide groups in the cuticle and induces apolysis, the separation of old and new cuticle, strongly suggesting that molting involves the regulated reduction of cuticle components driven by TRXR-1 and GSR-1. Using dauer larvae, we demonstrate that aged worms have a decreased capacity to molt, and decreased expression of GSR-1. Together, our results establish a function for the selenoprotein TRXR-1 and GSR-1 in the removal of old cuticle from the surface of epidermal cells.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-14973 (URN)10.1073/pnas.1006328108 (DOI)000286310300035 ()21199936 (PubMedID)2-s2.0-79551624525 (Scopus ID)
Available from: 2012-01-24 Created: 2012-01-24 Last updated: 2018-07-18Bibliographically approved
Senti, G., Ezcurra, M., Löbner, J., Schafer, W. R. & Swoboda, P. (2009). Worms With a Single Functional Sensory Cilium Generate Proper Neuron-Specific Behavioral Output. Genetics, 183(2), 595-605
Open this publication in new window or tab >>Worms With a Single Functional Sensory Cilium Generate Proper Neuron-Specific Behavioral Output
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2009 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 183, no 2, p. 595-605Article in journal (Refereed) Published
Abstract [en]

Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm Caenorhabditis elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSNs) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development., function, and behavior. We have generated a genetic rescue system that allows in vivo analyses of isolated CSNs at both cellular and systemic levels. We used the RFX transcription factor DAF-19, a key regulator of ciliogenesis. Mutations in daf-19 result in the complete absence of all sensory cilia and thus of external sensory input. In daf-19 mutants, we used cell-specific rescue of DAF-19 function in selected neurons, thereby generating animals with single, fully functional CSNs. Otherwise and elsewhere these animals are completely devoid of any environmental input through cilia. We demonstrated the rescue of fully functional, single cilia using fluorescent markers, sensory behavioral assays, and calcium imaging. Our technique, functional rescue in single sensory cilia (FRISSC), can thus cell-autonomously and cell-specifically restore the function of single sensory neurons and their ability to respond to sensory input. FRISSC can be adapted to many different CSNs and thus constitutes an excellent tool for studying sensory behaviors, both in single animals and in populations of worms. FRISSC will be Very useful for the molecular dissection of sensory perception in CSNs and for the analysis of the developmental aspects of ciliogenesis.

National Category
Genetics
Identifiers
urn:nbn:se:sh:diva-13882 (URN)10.1534/genetics.109.105171 (DOI)000271558300015 ()19652182 (PubMedID)2-s2.0-70649083251 (Scopus ID)
Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2018-07-18Bibliographically approved
Swoboda, P. (2009). Worms with only a single cilium S.: per animal. Paper presented at 16th Annual Conference of the International-Society-of-Development-Biologists, SEP 06-10, 2009, Edinburgh, SCOTLAND. Mechanisms of Development, 126, S17-S17
Open this publication in new window or tab >>Worms with only a single cilium S.: per animal
2009 (English)In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 126, p. S17-S17Article in journal, Meeting abstract (Refereed) Published
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-35660 (URN)10.1016/j.mod.2009.06.987 (DOI)000270034900044 ()
Conference
16th Annual Conference of the International-Society-of-Development-Biologists, SEP 06-10, 2009, Edinburgh, SCOTLAND
Available from: 2018-06-25 Created: 2018-06-25 Last updated: 2018-06-25Bibliographically approved
Li, C., Inglis, P. N., Leitch, C. C., Efimenko, E., Zaghloul, N. A., Mok, C. A., . . . Leroux, M. R. (2008). An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes. PLoS Genetics, 4(3), e1000044
Open this publication in new window or tab >>An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes
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2008 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 4, no 3, p. e1000044-Article in journal (Refereed) Published
Abstract [en]

MIP-T3 is a human protein found previously to associate with microtubules and the kinesin-interacting neuronal protein DISC1 ( Disrupted-in-Schizophrenia 1), but whose cellular function(s) remains unknown. Here we demonstrate that the C. elegans MIP-T3 ortholog DYF-11 is an intraflagellar transport (IFT) protein that plays a critical role in assembling functional kinesin motor-IFT particle complexes. We have cloned a loss of function dyf-11 mutant in which several key components of the IFT machinery, including Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised ciliary structures and sensory functions, and abnormal lipid accumulation. Analyses in different mutant backgrounds further suggest that DYF-11 functions as a novel component of IFT subcomplex B. Consistent with an evolutionarily conserved cilia-associated role, mammalian MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 functions synergistically with the Bardet-Biedl syndrome protein Bbs4 to ensure proper gastrulation, a key cilium- and basal body-dependent developmental process. Our findings therefore implicate MIP-T3 in a previously unknown but critical role in cilium biogenesis and further highlight the emerging role of this organelle in vertebrate development.

National Category
Genetics
Identifiers
urn:nbn:se:sh:diva-14165 (URN)10.1371/journal.pgen.1000044 (DOI)000255407300004 ()2-s2.0-41949085600 (Scopus ID)
Available from: 2011-12-18 Created: 2011-12-16 Last updated: 2018-07-18Bibliographically approved
Ceron, J. & Swoboda, P. (2008). Caenorhabditis elegans comes of age. Genome Biology, 9(6), 312
Open this publication in new window or tab >>Caenorhabditis elegans comes of age
2008 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 9, no 6, p. 312-Article in journal (Other academic) Published
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-14177 (URN)10.1186/gb-2008-9-6-312 (DOI)000257498000009 ()2-s2.0-50349101395 (Scopus ID)
Available from: 2011-12-18 Created: 2011-12-16 Last updated: 2018-07-18Bibliographically approved
Senti, G. & Swoboda, P. (2008). Distinct Isoforms of the RFX Transcription Factor DAF-19 Regulate Ciliogenesis and Maintenance of Synaptic Activity. Molecular Biology of the Cell, 19(12), 5517-5528
Open this publication in new window or tab >>Distinct Isoforms of the RFX Transcription Factor DAF-19 Regulate Ciliogenesis and Maintenance of Synaptic Activity
2008 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 19, no 12, p. 5517-5528Article in journal (Refereed) Published
Abstract [en]

Neurons form elaborate subcellular structures such as dendrites, axons, cilia, and synapses to receive signals from their environment and to transmit them to the respective target cells. In the worm Caenorhabditis elegans, lack of the RFX transcription factor DAF-19 leads to the absence of cilia normally found on 60 sensory neurons. We now describe and functionally characterize three different isoforms of DAF-19. The short isoform DAF-19C is specifically expressed in ciliated sensory neurons and sufficient to rescue all cilia-related phenotypes of daf-19 mutants. In contrast, the long isoforms DAF-19A/B function in basically all nonciliated neurons. We discovered behavioral and cellular phenotypes in daf-19 mutants that depend on the isoforms daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent of synaptic decline seen in many human neurodegenerative disorders. The C. elegans daf-19 mutant worms can thus serve as a molecular model for the mechanisms of functional neuronal decline.

National Category
Cell Biology
Identifiers
urn:nbn:se:sh:diva-14115 (URN)10.1091/mbc.E08-04-0416 (DOI)000261244700041 ()
Available from: 2011-12-18 Created: 2011-12-16 Last updated: 2018-07-18Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6416-8572

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