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  1. Article ; Online: Phosphate Limitation Responses in Marine Green Algae Are Linked to Reprogramming of the tRNA Epitranscriptome and Codon Usage Bias.

    Hehenberger, Elisabeth / Guo, Jian / Wilken, Susanne / Hoadley, Kenneth / Sudek, Lisa / Poirier, Camille / Dannebaum, Richard / Susko, Edward / Worden, Alexandra Z

    Molecular biology and evolution

    2023  Volume 40, Issue 12

    Abstract: Marine algae are central to global carbon fixation, and their productivity is dictated largely by resource availability. Reduced nutrient availability is predicted for vast oceanic regions as an outcome of climate change; however, there is much to learn ... ...

    Abstract Marine algae are central to global carbon fixation, and their productivity is dictated largely by resource availability. Reduced nutrient availability is predicted for vast oceanic regions as an outcome of climate change; however, there is much to learn regarding response mechanisms of the tiny picoplankton that thrive in these environments, especially eukaryotic phytoplankton. Here, we investigate responses of the picoeukaryote Micromonas commoda, a green alga found throughout subtropical and tropical oceans. Under shifting phosphate availability scenarios, transcriptomic analyses revealed altered expression of transfer RNA modification enzymes and biased codon usage of transcripts more abundant during phosphate-limiting versus phosphate-replete conditions, consistent with the role of transfer RNA modifications in regulating codon recognition. To associate the observed shift in the expression of the transfer RNA modification enzyme complement with the transfer RNAs encoded by M. commoda, we also determined the transfer RNA repertoire of this alga revealing potential targets of the modification enzymes. Codon usage bias was particularly pronounced in transcripts encoding proteins with direct roles in managing phosphate limitation and photosystem-associated proteins that have ill-characterized putative functions in "light stress." The observed codon usage bias corresponds to a proposed stress response mechanism in which the interplay between stress-induced changes in transfer RNA modifications and skewed codon usage in certain essential response genes drives preferential translation of the encoded proteins. Collectively, we expose a potential underlying mechanism for achieving growth under enhanced nutrient limitation that extends beyond the catalog of up- or downregulated protein-encoding genes to the cell biological controls that underpin acclimation to changing environmental conditions.
    MeSH term(s) Codon Usage ; Phosphates/metabolism ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Codon/genetics ; Codon/metabolism ; Chlorophyta/genetics ; Chlorophyta/metabolism ; Protein Biosynthesis
    Chemical Substances Phosphates ; RNA, Transfer (9014-25-9) ; Codon
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msad251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Phosphate limitation responses in marine green algae are linked to reprogramming of the tRNA epitranscriptome and codon usage bias

    Hehenberger, Elisabeth / Guo, Jian / Wilken, Susanne / Hoadley, Kenneth / Sudek, Lisa / Poirier, Camille / Dannebaum, Richard / Susko, Edward / Worden, Alexandra Z. / Agashe, Deepa

    2023  

    Abstract: Marine algae are central to global carbon fixation and their productivity is dictated largely by resource availability. Reduced nutrient availability is predicted for vast oceanic regions as an outcome of climate change, however there is much to learn ... ...

    Abstract Marine algae are central to global carbon fixation and their productivity is dictated largely by resource availability. Reduced nutrient availability is predicted for vast oceanic regions as an outcome of climate change, however there is much to learn regarding response mechanisms of the tiny picoplankton that thrive in these environments, especially eukaryotic phytoplankton. Here, we investigate responses of the picoeukaryote Micromonas commoda, a green alga found throughout subtropical and tropical oceans. Under shifting phosphate (P) availability scenarios, transcriptomic analyses revealed altered expression of transfer RNA (tRNA) modification enzymes and biased codon usage of transcripts more abundant during P-limiting versus P-replete conditions, consistent with the role of tRNA modifications in regulating codon recognition. To associate the observed shift in expression of the tRNA modification enzyme complement with the tRNAs encoded by M. commoda, we also determined the tRNA repertoire of this alga revealing potential targets of the modification enzymes. Codon usage bias was particularly pronounced in transcripts encoding proteins with direct roles in managing P-limitation and photosystem-associated proteins that have ill-characterized putative functions in “light stress”. The observed codon usage bias corresponds to a proposed stress response mechanism in which the interplay between stress-induced changes in tRNA modifications and skewed codon usage in certain essential response genes drives preferential translation of the encoded proteins. Collectively, we expose a potential underlying mechanism for achieving growth under enhanced nutrient limitation, that extends beyond the catalog of up- or down-regulated protein-encoding genes, to the cell biological controls that underpin acclimation to changing environmental conditions.
    Subject code 580
    Language English
    Publisher Oxford University Press
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Diverse mechanisms for spliceosome-mediated 3' end processing of telomerase RNA.

    Kannan, Ram / Helston, Rachel M / Dannebaum, Richard O / Baumann, Peter

    Nature communications

    2015  Volume 6, Page(s) 6104

    Abstract: The 3' end of Schizosaccharomyces pombe telomerase RNA (SpTER1) is generated by spliceosomal cleavage, a reaction that corresponds to the first step of splicing. The observation that the spliceosome functions in 3' end processing raised questions about ... ...

    Abstract The 3' end of Schizosaccharomyces pombe telomerase RNA (SpTER1) is generated by spliceosomal cleavage, a reaction that corresponds to the first step of splicing. The observation that the spliceosome functions in 3' end processing raised questions about the evolutionary origin and conservation of this mechanism. We now present data in support of spliceosomes generating 3' ends of telomerase RNAs in other fungi. Strikingly, the mechanistic basis for restricting spliceosomal splicing to the first transesterification reaction differs substantially among species. Unlike S. pombe, two other fission yeasts rely on hyperstabilization of the U6 snRNA-5' splice site interaction to impede the 2nd step of splicing. In contrast, a non-canonical 5' splice site blocks the second transesterification reaction in Aspergillus species. These results demonstrate a conserved role for spliceosomes functioning in 3' end processing. Divergent mechanisms of uncoupling the two steps of splicing argue for multiple origins of this pathway.
    MeSH term(s) Aspergillus/metabolism ; RNA/metabolism ; RNA Splicing ; RNA, Fungal/metabolism ; RNA, Small Nuclear/metabolism ; Schizosaccharomyces/metabolism ; Spliceosomes/metabolism ; Telomerase/metabolism
    Chemical Substances RNA, Fungal ; RNA, Small Nuclear ; telomerase RNA ; RNA (63231-63-0) ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2015-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms7104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.

    Dannebaum, Richard / Suwalski, Phillip / Asgharian, Hosseinali / Du Zhipei, Gracie / Lin, Hai / Weiner, January / Holtgrewe, Manuel / Thibeault, Charlotte / Müller, Melina / Wang, Xiaomin / Karadeniz, Zehra / Saccomanno, Jacopo / Doehn, Jan-Moritz / Hübner, Ralf-Harto / Hinzmann, Bernd / Blüher, Anja / Siemann, Sandra / Telman, Dilduz / Suttorp, Norbert /
    Witzenrath, Martin / Hippenstiel, Stefan / Skurk, Carsten / Poller, Wolfgang / Sander, Leif E / Beule, Dieter / Kurth, Florian / Guettouche, Toumy / Landmesser, Ulf / Berka, Jan / Luong, Khai / Rubelt, Florian / Heidecker, Bettina

    EClinicalMedicine

    2022  Volume 48, Page(s) 101438

    Abstract: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to ... ...

    Abstract Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response.
    Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19.
    Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression.
    Interpretation: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity.
    Funding: The study was funded with grants from the Berlin Institute of Health (BIH).
    Language English
    Publishing date 2022-05-14
    Publishing country England
    Document type Journal Article
    ISSN 2589-5370
    ISSN (online) 2589-5370
    DOI 10.1016/j.eclinm.2022.101438
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.

    Joseph, Magdalene / Wu, Yin / Dannebaum, Richard / Rubelt, Florian / Zlatareva, Iva / Lorenc, Anna / Du, Zhipei Gracie / Davies, Daniel / Kyle-Cezar, Fernanda / Das, Abhishek / Gee, Sarah / Seow, Jeffrey / Graham, Carl / Telman, Dilduz / Bermejo, Clara / Lin, Hai / Asgharian, Hosseinali / Laing, Adam G / Del Molino Del Barrio, Irene /
    Monin, Leticia / Muñoz-Ruiz, Miguel / McKenzie, Duncan R / Hayday, Thomas S / Francos-Quijorna, Isaac / Kamdar, Shraddha / Davis, Richard / Sofra, Vasiliki / Cano, Florencia / Theodoridis, Efstathios / Martinez, Lauren / Merrick, Blair / Bisnauthsing, Karen / Brooks, Kate / Edgeworth, Jonathan / Cason, John / Mant, Christine / Doores, Katie J / Vantourout, Pierre / Luong, Khai / Berka, Jan / Hayday, Adrian C

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 34, Page(s) e2201541119

    Abstract: Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based ... ...

    Abstract Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.
    MeSH term(s) Adaptive Immunity/genetics ; Aged ; B-Lymphocytes/immunology ; COVID-19/genetics ; COVID-19/immunology ; Genetic Loci ; Humans ; Immunoglobulin Heavy Chains/genetics ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; SARS-CoV-2/immunology ; Seroconversion ; T-Lymphocytes/immunology
    Chemical Substances Immunoglobulin Heavy Chains ; Receptors, Antigen, T-Cell ; Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2022-08-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2201541119
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  6. Article ; Online: Specialized proteomic responses and an ancient photoprotection mechanism sustain marine green algal growth during phosphate limitation.

    Guo, Jian / Wilken, Susanne / Jimenez, Valeria / Choi, Chang Jae / Ansong, Charles / Dannebaum, Richard / Sudek, Lisa / Milner, David S / Bachy, Charles / Reistetter, Emily Nahas / Elrod, Virginia A / Klimov, Denis / Purvine, Samuel O / Wei, Chia-Lin / Kunde-Ramamoorthy, Govindarajan / Richards, Thomas A / Goodenough, Ursula / Smith, Richard D / Callister, Stephen J /
    Worden, Alexandra Z

    Nature microbiology

    2018  Volume 3, Issue 7, Page(s) 781–790

    Abstract: Marine algae perform approximately half of global carbon fixation, but their growth is often limited by the availability of phosphate or other ... ...

    Abstract Marine algae perform approximately half of global carbon fixation, but their growth is often limited by the availability of phosphate or other nutrients
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bioreactors/parasitology ; Chlorophyta/classification ; Chlorophyta/growth & development ; Chlorophyta/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Phosphates/metabolism ; Photosynthesis ; Phylogeny ; Phytoplankton ; Proteomics/methods
    Chemical Substances Bacterial Proteins ; Phosphates
    Language English
    Publishing date 2018-06-25
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-018-0178-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19

    Richard Dannebaum / Phillip Suwalski / Hosseinali Asgharian / Gracie Du Zhipei / Hai Lin / January Weiner, 3rd / Manuel Holtgrewe / Charlotte Thibeault / Melina Müller / Xiaomin Wang / Zehra Karadeniz / Jacopo Saccomanno / Jan-Moritz Doehn / Ralf-Harto Hübner / Bernd Hinzmann / Anja Blüher / Sandra Siemann / Dilduz Telman / Norbert Suttorp /
    Martin Witzenrath / Stefan Hippenstiel / Carsten Skurk / Wolfgang Poller / Leif E Sander / Dieter Beule / Florian Kurth / Toumy Guettouche / Ulf Landmesser / Jan Berka / Khai Luong / Florian Rubelt / Bettina Heidecker

    EClinicalMedicine, Vol 48, Iss , Pp 101438- (2022)

    2022  

    Abstract: Summary: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to ...

    Abstract Summary: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple ...
    Keywords COVID-19 ; Immune repertoires ; Immune receptor ; Clinical course ; Medicine (General) ; R5-920
    Subject code 610 ; 616
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Widespread adenine N6-methylation of active genes in fungi.

    Mondo, Stephen J / Dannebaum, Richard O / Kuo, Rita C / Louie, Katherine B / Bewick, Adam J / LaButti, Kurt / Haridas, Sajeet / Kuo, Alan / Salamov, Asaf / Ahrendt, Steven R / Lau, Rebecca / Bowen, Benjamin P / Lipzen, Anna / Sullivan, William / Andreopoulos, Bill B / Clum, Alicia / Lindquist, Erika / Daum, Christopher / Northen, Trent R /
    Kunde-Ramamoorthy, Govindarajan / Schmitz, Robert J / Gryganskyi, Andrii / Culley, David / Magnuson, Jon / James, Timothy Y / O'Malley, Michelle A / Stajich, Jason E / Spatafora, Joseph W / Visel, Axel / Grigoriev, Igor V

    Nature genetics

    2017  Volume 49, Issue 6, Page(s) 964–968

    Abstract: N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that ... ...

    Abstract N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages. Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes.
    MeSH term(s) 5-Methylcytosine/metabolism ; Adenine/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Fungi/genetics ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Phylogeny ; Transcription Initiation Site
    Chemical Substances 5-Methylcytosine (6R795CQT4H) ; Adenine (JAC85A2161)
    Language English
    Publishing date 2017-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3859
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  9. Article ; Online: Specialized proteomic responses and an ancient photoprotection mechanism sustain marine green algal growth during phosphate limitation

    Guo, J. / Wilken, S. / Jimenez, V. / Choi, C. J. / Ansong, C. / Dannebaum, R. / Sudek, L. / Milner, D. S. / Bachy, C. / Reistetter, E. N. / Elrod, V. A. / Klimov, D. / Purvine, S. O. / Wei, C.-L. / Kunde-Ramamoorthy, G. / Richards, T. A. / Goodenough, U. / Smith, R. D. / Callister, S. J. /
    Worden, Alexandra Z.

    2018  

    Abstract: Marine algae perform approximately half of global carbon fixation, but their growth is often limited by the availability of phosphate or other nutrients 1,2 . As oceans warm, the area of phosphate-limited surface waters is predicted to increase, ... ...

    Abstract Marine algae perform approximately half of global carbon fixation, but their growth is often limited by the availability of phosphate or other nutrients 1,2 . As oceans warm, the area of phosphate-limited surface waters is predicted to increase, resulting in ocean desertification 3,4 . Understanding the responses of key eukaryotic phytoplankton to nutrient limitation is therefore critical 5,6 . We used advanced photo-bioreactors to investigate how the widespread marine green alga Micromonas commoda grows under transitions from replete nutrients to chronic phosphate limitation and subsequent relief, analysing photosystem changes and broad cellular responses using proteomics, transcriptomics and biophysical measurements. We find that physiological and protein expression responses previously attributed to stress are critical to supporting stable exponential growth when phosphate is limiting. Unexpectedly, the abundance of most proteins involved in light harvesting does not change, but an ancient light-harvesting-related protein, LHCSR, is induced and dissipates damaging excess absorbed light as heat throughout phosphate limitation. Concurrently, a suite of uncharacterized proteins with narrow phylogenetic distributions increase multifold. Notably, of the proteins that exhibit significant changes, 70 are not differentially expressed at the mRNA transcript level, highlighting the importance of post-transcriptional processes in microbial eukaryotes. Nevertheless, transcript-protein pairs with concordant changes were identified that will enable more robust interpretation of eukaryotic phytoplankton responses in the field from metatranscriptomic studies. Our results show that P-limited Micromonas responds quickly to a fresh pulse of phosphate by rapidly increasing replication, and that the protein network associated with this ability is composed of both conserved and phylogenetically recent proteome systems that promote dynamic phosphate homeostasis. That an ancient mechanism for mitigating light stress is central to ...
    Subject code 551
    Language English
    Publisher Nature Research
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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