Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Johansson, Marcus J. O.
Alternative names
Publications (10 of 23) Show all publications
Rosendahl, S., Sulniute, R., Eklund, M., Holm, C. K., Johansson, M. J. O., Kindstedt, E., . . . Lundberg, P. (2021). CCR3 deficiency is associated with increased osteoclast activity and reduced cortical bone volume in adult male mice. Journal of Biological Chemistry, 296, Article ID 100177.
Open this publication in new window or tab >>CCR3 deficiency is associated with increased osteoclast activity and reduced cortical bone volume in adult male mice
Show others...
2021 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 296, article id 100177Article in journal (Refereed) Published
Abstract [en]

Increasing evidence emphasizes the importance of chemokines and chemokine receptors as regulators of bone remodeling. The C–C chemokine receptor 3 (CCR3) is dramatically upregulated during osteoclastogenesis, but the role of CCR3 in osteoclast formation and bone remodeling in adult mice is unknown. Herein, we used bone marrow macrophages derived from adult male CCR3-proficient and CCR3-deficient mice to study the role of CCR3 in osteoclast formation and activity. CCR3 deficiency was associated with formation of giant hypernucleated osteoclasts, enhanced bone resorption when cultured on bone slices, and altered mRNA expression of related chemokine receptors and ligands. In addition, primary mouse calvarial osteoblasts isolated from CCR3-deficient mice showed increased mRNA expression of the osteoclast activator–related gene, receptor activator of nuclear factor kappa-B ligand, and osteoblast differentiation–associated genes. Microcomputed tomography analyses of femurs from CCR3-deficient mice revealed a bone phenotype that entailed less cortical thickness and volume. Consistent with our in vitro studies, the total number of osteoclasts did not differ between the genotypes in vivo. Moreover, an increased endocortical osteoid mineralization rate and higher trabecular and cortical bone formation rate was displayed in CCR3-deficient mice. Collectively, our data show that CCR3 deficiency influences osteoblast and osteoclast differentiation and that it is associated with thinner cortical bone in adult male mice.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2021
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-182038 (URN)10.1074/jbc.RA120.015571 (DOI)000672866400155 ()33303631 (PubMedID)2-s2.0-85102806599 (Scopus ID)
Available from: 2021-04-21 Created: 2021-04-21 Last updated: 2023-09-05Bibliographically approved
Xu, F., Byström, A. & Johansson, M. J. O. (2020). SSD1 modifies phenotypes of Elongator mutants. Current Genetics, 66, 481-485
Open this publication in new window or tab >>SSD1 modifies phenotypes of Elongator mutants
2020 (English)In: Current Genetics, ISSN 0172-8083, E-ISSN 1432-0983, Vol. 66, p. 481-485Article, review/survey (Refereed) Published
Abstract [en]

The translational decoding properties of tRNAs are influenced by post-transcriptional modification of nucleosides in their anticodon region. The Elongator complex promotes the first step in the formation of 5-methoxycarbonylmethyl (mcm(5)), 5-methoxycarbonylhydroxymethyl (mchm(5)), and 5-carbamoylmethyl (ncm(5)) groups on wobble uridine residues in eukaryotic cytosolic tRNAs. Elongator mutants in yeast, worms, plants, mice, and humans not only show a tRNA modification defect, but also a diverse range of additional phenotypes. Even though the phenotypes are almost certainly caused by the reduced functionality of the hypomodified tRNAs in translation, the basis for specific phenotypes is not well understood. Here, we discuss the recent finding that the phenotypes of Saccharomyces cerevisiae Elongator mutants are modulated by the genetic background. This background-effect is largely due to the allelic variation at the SSD1 locus, which encodes an mRNA-binding protein involved in post-transcriptional regulation of gene expression. A nonsense ssd1 allele is found in several wild-type laboratory strains and the presence of this allele aggravates the stress-induced phenotypes of Elongator mutants. Moreover, other phenotypes, such as the histone acetylation and telomeric gene silencing defects, are dependent on the mutant ssd1 allele. Thus, SSD1 is a genetic modifier of the phenotypes of Elongator-deficient yeast cells.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2020
Keywords
Elongator complex, tRNA modification, Translation, mRNA-binding protein
National Category
Biochemistry and Molecular Biology Genetics
Identifiers
urn:nbn:se:umu:diva-166507 (URN)10.1007/s00294-019-01048-9 (DOI)000498973600001 ()31776648 (PubMedID)2-s2.0-85075611494 (Scopus ID)
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2020-08-07Bibliographically approved
Kasari, V., Pochopien, A. A., Margus, T., Murina, V., Turnbull, K. J., Zhou, Y., . . . Hauryliuk, V. (2019). A role for the Saccharomyces cerevisiae ABCF protein New1 in translation termination/recycling. Nucleic Acids Research, 47(16), 8807-8820
Open this publication in new window or tab >>A role for the Saccharomyces cerevisiae ABCF protein New1 in translation termination/recycling
Show others...
2019 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 47, no 16, p. 8807-8820Article in journal (Refereed) Published
Abstract [en]

Translation is controlled by numerous accessory proteins and translation factors. In the yeast Saccharomyces cerevisiae, translation elongation requires an essential elongation factor, the ABCF ATPase eEF3. A closely related protein, New1, is encoded by a non-essential gene with cold sensitivity and ribosome assembly defect knock-out phenotypes. Since the exact molecular function of New1 is unknown, it is unclear if the ribosome assembly defect is direct, i.e. New1 is a bona fide assembly factor, or indirect, for instance due to a defect in protein synthesis. To investigate this, we employed yeast genetics, cryo-electron microscopy (cryo-EM) and ribosome profiling (Ribo-Seq) to interrogate the molecular function of New1. Overexpression of New1 rescues the inviability of a yeast strain lacking the otherwise strictly essential translation factor eEF3. The structure of the ATPase-deficient (EQ2) New1 mutant locked on the 80S ribosome reveals that New1 binds analogously to the ribosome as eEF3. Finally, Ribo-Seq analysis revealed that loss of New1 leads to ribosome queuing upstream of 3′-terminal lysine and arginine codons, including those genes encoding proteins of the cytoplasmic translational machinery. Our results suggest that New1 is a translation factor that fine-tunes the efficiency of translation termination or ribosome recycling.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-164896 (URN)10.1093/nar/gkz600 (DOI)000490576900040 ()31299085 (PubMedID)2-s2.0-85073311572 (Scopus ID)
Funder
Swedish Research Council, 2017-03783Swedish Research Council, 201504746Swedish Research Council, 2017-04663Ragnar Söderbergs stiftelseThe Kempe Foundations, JCK1627The Kempe Foundations, SMK-1349Magnus Bergvall Foundation, 2017-02098Åke Wiberg Foundation, M14-0207EU, Horizon 2020, 2643Swedish Research Council, 2017-03783
Available from: 2019-11-05 Created: 2019-11-05 Last updated: 2023-03-24Bibliographically approved
Kasari, V., Margus, T., Atkinson, G. C., Johansson, M. J. O. & Hauryliuk, V. (2019). Ribosome profiling analysis of eEF3-depleted Saccharomyces cerevisiae. Scientific Reports, 9, Article ID 3037.
Open this publication in new window or tab >>Ribosome profiling analysis of eEF3-depleted Saccharomyces cerevisiae
Show others...
2019 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 3037Article in journal (Refereed) Published
Abstract [en]

In addition to the standard set of translation factors common in eukaryotic organisms, protein synthesis in the yeast Saccharomyces cerevisiae requires an ABCF ATPase factor eEF3, eukaryotic Elongation Factor 3. eEF3 is an E-site binder that was originally identified as an essential factor involved in the elongation stage of protein synthesis. Recent biochemical experiments suggest an additional function of eEF3 in ribosome recycling. We have characterised the global effects of eEF3 depletion on translation using ribosome profiling. Depletion of eEF3 results in decreased ribosome density at the stop codon, indicating that ribosome recycling does not become rate limiting when eEF3 levels are low. Consistent with a defect in translation elongation, eEF3 depletion causes a moderate redistribution of ribosomes towards the 5' part of the open reading frames. We observed no E-site codon-or amino acid-specific ribosome stalling upon eEF3 depletion, supporting its role as a general elongation factor. Surprisingly, depletion of eEF3 leads to a relative decrease in P-site proline stalling, which we hypothesise is a secondary effect of generally decreased translation and/or decreased competition for the E-site with eIF5A.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-157582 (URN)10.1038/s41598-019-39403-y (DOI)000459891700047 ()30816176 (PubMedID)2-s2.0-85062273271 (Scopus ID)
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2023-03-24Bibliographically approved
Xu, F., Byström, A. & Johansson, M. J. O. (2019). SSD1 suppresses phenotypes induced by the lack of Elongator-dependent tRNA modifications. PLOS Genetics, 15(8), Article ID e1008117.
Open this publication in new window or tab >>SSD1 suppresses phenotypes induced by the lack of Elongator-dependent tRNA modifications
2019 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, no 8, article id e1008117Article in journal (Refereed) Published
Abstract [en]

The Elongator complex promotes formation of 5-methoxycarbonylmethyl (mcm5 ) and 5-carbamoylmethyl (ncm5 ) side-chains on uridines at the wobble position of cytosolic eukaryotic tRNAs. In all eukaryotic organisms tested to date, the inactivation of Elongator not only leads to the lack of mcm5 /ncm5 groups in tRNAs, but also a wide variety of additional phenotypes. Although the phenotypes are most likely caused by a translational defect induced by reduced functionality of the hypomodified tRNAs, the mechanism(s) underlying individual phenotypes are poorly understood. In this study, we show that the genetic background modulates the phenotypes induced by the lack of mcm5 /ncm5 groups in Saccharomyces cerevisiae. We show that the stress-induced growth defects of Elongator mutants are stronger in the W303 than in the closely related S288C genetic background and that the phenotypic differences are caused by the known polymorphism at the locus for the mRNA binding protein Ssd1. Moreover, the mutant ssd1 allele found in W303 cells is required for the reported histone H3 acetylation and telomeric gene silencing defects of Elongator mutants. The difference at the SSD1 locus also partially explains why the simultaneous lack of mcm5 and 2- thio groups at wobble uridines is lethal in the W303 but not in the S288C background. Collectively, our results demonstrate that the SSD1 locus modulates phenotypes induced by the lack of Elongator-dependent tRNA modifications.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2019
National Category
Cell and Molecular Biology Medical Genetics
Identifiers
urn:nbn:se:umu:diva-164426 (URN)10.1371/journal.pgen.1008117 (DOI)000486222200003 ()31465447 (PubMedID)2-s2.0-85072133857 (Scopus ID)
Available from: 2019-10-22 Created: 2019-10-22 Last updated: 2023-03-24Bibliographically approved
Brodiazhenko, T., Johansson, M. J. O., Takada, H., Nissan, T., Hauryliuk, V. & Murina, V. (2018). Elimination of Ribosome Inactivating Factors Improves the Efficiency of Bacillus subtilis and Saccharomyces cerevisiae Cell-Free Translation Systems. Frontiers in Microbiology, 9, Article ID 3041.
Open this publication in new window or tab >>Elimination of Ribosome Inactivating Factors Improves the Efficiency of Bacillus subtilis and Saccharomyces cerevisiae Cell-Free Translation Systems
Show others...
2018 (English)In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 9, article id 3041Article in journal (Refereed) Published
Abstract [en]

Cell-free translation systems based on cellular lysates optimized for in vitro protein synthesis have multiple applications both in basic and applied science, ranging from studies of translational regulation to cell-free production of proteins and ribosome-nascent chain complexes. In order to achieve both high activity and reproducibility in a translation system, it is essential that the ribosomes in the cellular lysate are enzymatically active. Here we demonstrate that genomic disruption of genes encoding ribosome inactivating factors – HPF in Bacillus subtilis and Stm1 in Saccharomyces cerevisiae – robustly improve the activities of bacterial and yeast translation systems. Importantly, the elimination of B. subtilis HPF results in a complete loss of 100S ribosomes, which otherwise interfere with disome-based approaches for preparation of stalled ribosomal complexes for cryo-electron microscopy studies.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
HPF, Stm1, Bacillus subtilis, Saccharomyces cerevisiae, cell-tree translation system
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-155100 (URN)10.3389/fmicb.2018.03041 (DOI)000453653000001 ()2-s2.0-85082559395 (Scopus ID)
Funder
Swedish Research Council, 2013-4680Swedish Research Council, 2017-04663Ragnar Söderbergs stiftelseMagnus Bergvall Foundation, 2017-02098Åke Wiberg Foundation, M14-0207
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2024-01-17Bibliographically approved
Johansson, M. J., Xu, F. & Byström, A. S. (2018). Elongator-a tRNA modifying complex that promotes efficient translational decoding. Biochimica et Biophysica Acta, 1861(4), 401-408
Open this publication in new window or tab >>Elongator-a tRNA modifying complex that promotes efficient translational decoding
2018 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1861, no 4, p. 401-408Article in journal (Refereed) Published
Abstract [en]

Naturally occurring modifications of the nucleosides in the anticodon region of tRNAs influence their translational decoding properties. Uridines present at the wobble position in eukaryotic cytoplasmic tRNAs often contain a 5-carbamoylmethyl (ncm5) or 5-methoxycarbonylmethyl (mcm5) side-chain and sometimes also a 2-thio or 2'-O-methyl group. The first step in the formation of the ncm5 and mcm5 side-chains requires the conserved six-subunit Elongator complex. Although Elongator has been implicated in several different cellular processes, accumulating evidence suggests that its primary, and possibly only, cellular function is to promote modification of tRNAs. In this review, we discuss the biosynthesis and function of modified wobble uridines in eukaryotic cytoplasmic tRNAs, focusing on the in vivo role of Elongator-dependent modifications in Saccharomyces cerevisiae. 

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-147685 (URN)10.1016/j.bbagrm.2017.11.006 (DOI)000430523900013 ()29170010 (PubMedID)2-s2.0-85034852019 (Scopus ID)
Funder
Swedish Research Council, 621-2016-03949
Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2023-03-24Bibliographically approved
Xu, F., Zhou, Y., Byström, A. & Johansson, M. J. O. (2018). Identification of factors that promote biogenesis of tRNACGASer. RNA Biology, 15(10), 1286-1294
Open this publication in new window or tab >>Identification of factors that promote biogenesis of tRNACGASer
2018 (English)In: RNA Biology, ISSN 1547-6286, E-ISSN 1555-8584, Vol. 15, no 10, p. 1286-1294Article in journal (Refereed) Published
Abstract [en]

A wide variety of factors are required for the conversion of pre-tRNA molecules into the mature tRNAs that function in translation. To identify factors influencing tRNA biogenesis, we previously performed a screen for strains carrying mutations that induce lethality when combined with a sup61-T47:2C allele, encoding a mutant form of tRNACGASer. Analyzes of two complementation groups led to the identification of Tan1 as a protein involved in formation of the modified nucleoside N4-acetylcytidine (ac4C) in tRNA and Bud13 as a factor controlling the levels of ac4C by promoting TAN1 pre-mRNA splicing. Here, we describe the remaining complementation groups and show that they include strains with mutations in genes for known tRNA biogenesis factors that modify (DUS2, MOD5 and TRM1), transport (LOS1), or aminoacylate (SES1) tRNACGASer. Other strains carried mutations in genes for factors involved in rRNA/mRNA synthesis (RPA49, RRN3 and MOT1) or magnesium uptake (ALR1). We show that mutations in not only DUS2, LOS1 and SES1 but also in RPA49, RRN3 and MOT1 cause a reduction in the levels of the altered tRNACGASer. These results indicate that Rpa49, Rrn3 and Mot1 directly or indirectly influence tRNACGASer biogenesis.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
modified nucleosides, sup61, tRNA maturation, tRNA modification, tRNASer
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-154010 (URN)10.1080/15476286.2018.1526539 (DOI)000450608900004 ()30269676 (PubMedID)2-s2.0-85055593077 (Scopus ID)
Funder
Magnus Bergvall Foundation, 2017-02098Swedish Research Council, 621-2016-03949
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2023-03-24Bibliographically approved
Johansson, M. J. (2017). Determining if an mRNA is a Substrate of Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae. Methods in Molecular Biology, 1507, 169-177
Open this publication in new window or tab >>Determining if an mRNA is a Substrate of Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae
2017 (English)In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1507, p. 169-177Article in journal (Refereed) Published
Abstract [en]

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic quality control mechanism which triggers decay of mRNAs harboring premature translation termination codons. In this chapter, I describe methods for monitoring the influence of NMD on mRNA abundance and decay rates in Saccharomyces cerevisiae. The descriptions include detailed methods for growing yeast cells, total RNA isolation, and Northern blotting. Although the chapter focuses on NMD, the methods can be easily adapted to assess the effect of other mRNA decay pathways.

Keywords
Half-lives, NMD, Northern blotting, RNA isolation, Yeast, mRNA decay, mRNA levels
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-135240 (URN)10.1007/978-1-4939-6518-2_13 (DOI)27832540 (PubMedID)2-s2.0-84994908518 (Scopus ID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2023-03-24Bibliographically approved
Zhou, Y. & Johansson, M. J. (2017). The pre-mRNA retention and splicing complex controls expression of the Mediator subunit Med20. RNA Biology, 14(10), 1411-1417
Open this publication in new window or tab >>The pre-mRNA retention and splicing complex controls expression of the Mediator subunit Med20
2017 (English)In: RNA Biology, ISSN 1547-6286, E-ISSN 1555-8584, Vol. 14, no 10, p. 1411-1417Article in journal (Refereed) Published
Abstract [en]

The heterotrimeric pre-mRNA retention and splicing (RES) complex, consisting of Bud13p, Snu17p and Pml1p, promotes splicing and nuclear retention of a subset of intron-containing pre-mRNAs. Yeast cells deleted for individual RES genes show growth defects that are exacerbated at elevated temperatures. Although the growth phenotypes correlate to the splicing defects in the individual mutants, the underlying mechanism is unknown. Here, we show that the temperature sensitive (Ts) growth phenotype of bud13Δ and snu17Δ cells is a consequence of inefficient splicing of MED20 pre-mRNA, which codes for a subunit of the Mediator complex; a co-regulator of RNA polymerase II transcription. The MED20 pre-mRNA splicing defect is less pronounced in pml1Δ cells, explaining why they grow better than the other 2 RES mutants at elevated temperatures. Inactivation of the cytoplasmic nonsense-mediated mRNA decay (NMD) pathway in the RES mutants leads to accumulation of MED20 pre-mRNA, indicating that inefficient nuclear retention contributes to the growth defect. Further, the Ts phenotype of bud13Δ and snu17Δ cells is partially suppressed by the inactivation of NMD, showing that the growth defects are augmented by the presence of a functional NMD pathway. Collectively, our results demonstrate an important role of the RES complex in maintaining the Med20p levels.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Med20, NMD, RES complex, mediator, splicing
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-135241 (URN)10.1080/15476286.2017.1294310 (DOI)000418050000015 ()28277935 (PubMedID)2-s2.0-85015637678 (Scopus ID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2023-03-24Bibliographically approved
Organisations

Search in DiVA

Show all publications