scholarly journals Analysis of the TORC1 interactome reveals a spatially distinct function of TORC1 in mRNP complexes

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Yeonji Chang ◽  
Gyubum Lim ◽  
Won-Ki Huh
Keyword(s):  
Posttranscriptional Regulation ◽  
Eukaryotic Cell ◽  
Vacuolar Membrane ◽  
Bimolecular Fluorescence Complementation ◽  
Functional Roles ◽  
Translational Repressor ◽  
Mrna Metabolism ◽  
Specific Subset ◽  
Messenger Ribonucleoprotein ◽  
A Genome

The target of rapamycin complex 1 (TORC1) is mainly localized to the vacuolar membrane and regulates eukaryotic cell growth in response to nutrient availability. To obtain deeper insights into the functional roles of TORC1, we performed a genome-wide analysis of the TORC1 interactome in yeast using the bimolecular fluorescence complementation (BiFC) assay. We found that while most of the BiFC signals are observed at the vacuolar membrane, a fraction of them are detected at cytoplasmic messenger ribonucleoprotein (mRNP) granules. Moreover, mRNA-binding proteins are enriched in the TORC1 interactome, suggesting a functional relationship between TORC1 and mRNA metabolism. We show that a portion of TORC1 is consistently associated with mRNP complexes and interacts with a specific subset of mRNAs. We also demonstrate that TORC1 directly targets a translational repressor Scd6 and that the activity of Scd6 is inhibited by TORC1-dependent phosphorylation. Collectively, our data suggest that TORC1 plays a novel role in posttranscriptional regulation by controlling the activity of Scd6.

scholarly journals Nuclear Gene Dosage Effects Upon the Expression of Maize Mitochondrial Genes

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1711-1721
Author(s):  
Donald L Auger ◽  
Kathleen J Newton ◽  
James A Birchler
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Gene Dosage ◽  
Nuclear Gene ◽  
Eukaryotic Cell ◽  
Mitochondrial Genes ◽  
Northern Analysis ◽  
Α Subunit ◽  
Dosage Effects ◽  
A Genome

Abstract Each mitochondrion possesses a genome that encodes some of its own components. The nucleus encodes most of the mitochondrial proteins, including the polymerases and factors that regulate the expression of mitochondrial genes. Little is known about the number or location of these nuclear factors. B-A translocations were used to create dosage series for 14 different chromosome arms in maize plants with normal cytoplasm. The presence of one or more regulatory factors on a chromosome arm was indicated when variation of its dosage resulted in the alteration in the amount of a mitochondrial transcript. We used quantitative Northern analysis to assay the transcript levels of three mitochondrially encoded components of the cytochrome c oxidase complex (cox1, cox2, and cox3). Data for a nuclearly encoded component (cox5b) and for two mitochondrial genes that are unrelated to cytochrome c oxidase, ATP synthase α-subunit and 18S rRNA, were also determined. Two tissues, embryo and endosperm, were compared and most effects were found to be tissue specific. Significantly, the array of dosage effects upon mitochondrial genes was similar to what had been previously found for nuclear genes. These results support the concept that although mitochondrial genes are prokaryotic in origin, their regulation has been extensively integrated into the eukaryotic cell.

scholarly journals Additional Layer of Regulation via Convergent Gene Orientation in Yeasts

2019 ◽  
Vol 37 (2) ◽  
pp. 365-378 ◽  
Author(s):  
Jules Gilet ◽  
Romain Conte ◽  
Claire Torchet ◽  
Lionel Benard ◽  
Ingrid Lafontaine
Keyword(s):  
Posttranscriptional Regulation ◽  
Additional Layer ◽  
Complementary Sequences ◽  
Gene Orientation ◽  
Genome Wide ◽  
Messenger Ribonucleoprotein ◽  
Binding Preference ◽  
Additional Level ◽  
Duplex Formation

Abstract Convergent gene pairs can produce transcripts with complementary sequences. We had shown that mRNA duplexes form in vivo in Saccharomyces cerevisiae via interactions of mRNA overlapping 3′-ends and can lead to posttranscriptional regulatory events. Here we show that mRNA duplex formation is restricted to convergent genes separated by short intergenic distance, independently of their 3′-untranslated region (UTR) length. We disclose an enrichment in genes involved in biological processes related to stress among these convergent genes. They are markedly conserved in convergent orientation in budding yeasts, meaning that this mode of posttranscriptional regulation could be shared in these organisms, conferring an additional level for modulating stress response. We thus investigated the mechanistic advantages potentially conferred by 3′-UTR mRNA interactions. Analysis of genome-wide transcriptome data revealed that Pat1 and Lsm1 factors, having 3′-UTR binding preference and participating to the remodeling of messenger ribonucleoprotein particles, bind differently these messenger-interacting mRNAs forming duplexes in comparison to mRNAs that do not interact (solo mRNAs). Functionally, messenger-interacting mRNAs show limited translational repression upon stress. We thus propose that mRNA duplex formation modulates the regulation of mRNA expression by limiting their access to translational repressors. Our results thus show that posttranscriptional regulation is an additional factor that determines the order of coding genes.

scholarly journals Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

2016 ◽  
Author(s):  
Bony De Kumar ◽  
Hugo J. Parker ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Irina Pushel ◽  
...  
Keyword(s):  
Es Cells ◽  
Hox Proteins ◽  
Binding Motifs ◽  
Functional Roles ◽  
Regulatory Interactions ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
A Genome ◽  
Combinatorial Interactions ◽  
Insight Into

AbstractHoxa1 has diverse functional roles in differentiation and development. We have identified and characterized properties of regions bound by Hoxa1 on a genome-wide basis in differentiating mouse ES cells. Hoxa1 bound regions are enriched for clusters of consensus binding motifs for Hox, Pbx and Meis and many display co-occupancy of Pbx and Meis. Pbx and Meis are members of the TALE family and genome-wide analysis of multiple TALE members (Pbx, Meis, TGIF, Prep1 and Prep2) show that nearly all Hoxa1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins defines distinct classes of Hoxa1 targets and indicates a role as cofactors in modulating the specificity of Hox proteins. We also discovered extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes. This study provides new insight into a regulatory network involving combinatorial interactions between Hoxa1 and TALE proteins.

Molecular dissection of a genome defense pathway in Neurospora crassa

2015 ◽  
Author(s):  
◽  
Erin C. Boone
Keyword(s):  
Neurospora Crassa ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Periphery ◽  
Bimolecular Fluorescence Complementation ◽  
Proper Function ◽  
Rnai Pathway ◽  
Binding Motif ◽  
Perinuclear Region ◽  
A Genome

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Meiotic silencing by unpaired DNA (MSUD) is an RNA interference (RNAi) pathway in Neurospora crassa that detects genes without a homologous partner and silences them for the duration of sexual development. In this study, we have further elucidated the function of known MSUD proteins, identified novel proteins that are required for MSUD, and demonstrated the conservation of RNAi-related processes at the nuclear periphery. We began by showing SAD-2 is crucial for the localization of other MSUD proteins in the perinuclear region. These data suggest that SAD-2 works as a scaffold protein and that proper function of MSUD, like other germline RNAi-like systems, is reliant on the presence of silencing proteins in the perinuclear region. An MSUD suppression assay identified two novel MSUD proteins, SAD-Y and SAD-B'. Even though SAD-Y and its homologs contain a conserved putative RNA- binding motif, they have yet to be assigned to a biochemical pathway. Our work here has linked silencing to SAD-Y-like proteins. SAD-Y has been shown to interact with other MSUD factors in both the nucleus and at the nuclear periphery. SAD-B's homolog has been found in the nuage, an epicenter for RNA-binding proteins involved in post-transcriptional regulation for Drosophila germline cells. SAD-B interacts with core MSUD proteins and has an especially intimate association with SMS-2, which requires it for localization. Furthermore, bimolecular fluorescence complementation (BiFC) revealed that SAD-B' interacts with a Golgi retrograde transport protein and an autophagy marker protein, suggesting the importance of the endomembrane system in this RNAi process.

scholarly journals SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Maribel Aguilar-Medina ◽  
Mariana Avendaño-Félix ◽  
Erik Lizárraga-Verdugo ◽  
Mercedes Bermúdez ◽  
José Geovanni Romero-Quintana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Current Knowledge ◽  
Functional Roles ◽  
Novel Treatments ◽  
Specific Subset ◽  
Different Types ◽  
Undifferentiated Cells ◽  
Functional Relevance

Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.

scholarly journals Whole-genome screening identifies proteins localized to distinct nuclear bodies

2013 ◽  
Vol 203 (1) ◽  
pp. 149-164 ◽  
Author(s):  
Ka-wing Fong ◽  
Yujing Li ◽  
Wenqi Wang ◽  
Wenbin Ma ◽  
Kunpeng Li ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Nuclear Bodies ◽  
Cajal Bodies ◽  
Nuclear Speckles ◽  
Genome Wide ◽  
A Genome ◽  
Human Proteins ◽  
Genome Screening ◽  
Interchromatin Space ◽  
Polycomb Bodies

The nucleus is a unique organelle that contains essential genetic materials in chromosome territories. The interchromatin space is composed of nuclear subcompartments, which are defined by several distinctive nuclear bodies believed to be factories of DNA or RNA processing and sites of transcriptional and/or posttranscriptional regulation. In this paper, we performed a genome-wide microscopy-based screening for proteins that form nuclear foci and characterized their localizations using markers of known nuclear bodies. In total, we identified 325 proteins localized to distinct nuclear bodies, including nucleoli (148), promyelocytic leukemia nuclear bodies (38), nuclear speckles (27), paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodies (5), Polycomb bodies (2), and uncharacterized nuclear bodies (64). Functional validation revealed several proteins potentially involved in the assembly of Cajal bodies and paraspeckles. Together, these data establish the first atlas of human proteins in different nuclear bodies and provide key information for research on nuclear bodies.

scholarly journals Mitochondria and hydrogenosomes are two forms of the same fundamental organelle

2003 ◽  
Vol 358 (1429) ◽  
pp. 191-203 ◽  
Author(s):  
Martin Embley ◽  
Mark van der Giezen ◽  
David S. Horner ◽  
Patricia L. Dyal ◽  
Peter Foster
Keyword(s):  
Early Stage ◽  
Phylogenetic Analyses ◽  
Eukaryotic Cell ◽  
Published Data ◽  
Ferredoxin Oxidoreductase ◽  
Cell Compartments ◽  
Microbial Eukaryotes ◽  
A Genome ◽  
Different Types ◽  
Pyruvate Ferredoxin Oxidoreductase

Published data suggest that hydrogenosomes, organelles found in diverse anaerobic eukaryotes that make energy and hydrogen, were once mitochondria. As hydrogenosomes generally lack a genome, the conversion is probably one way. The sources of the key hydrogenosomal enzymes, pyruvate : ferredoxin oxidoreductase (PFO) and hydrogenase, are not resolved by current phylogenetic analyses, but it is likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobic eukaryotes, the proteins are intimately integrated into the fabric of diverse eukaryotic cells, where they are targeted to different cell compartments, and not just hydrogenosomes. There is no evidence supporting the view that PFO and hydrogenase originated from the mitochondrial endosymbiont, as posited by the hydrogen hypothesis for eukaryogenesis. Other organelles derived from mitochondria have now been described in anaerobic and parasitic microbial eukaryotes, including species that were once thought to have diverged before the mitochondrial symbiosis. It thus seems possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, to which different types of biochemistry can be targeted. It remains to be seen if, despite their obvious differences, this family of organelles shares a common function of importance for the eukaryotic cell, other than energy production, that might provide the underlying selection pressure for organelle retention.

scholarly journals Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3239
Author(s):  
Zaur M. Kachaev ◽  
Sergey D. Ivashchenko ◽  
Eugene N. Kozlov ◽  
Lyubov A. Lebedeva ◽  
Yulii V. Shidlovskii
Keyword(s):  
Gene Expression ◽  
Cell Nucleus ◽  
Ribosomal Proteins ◽  
Nuclear Translocation ◽  
Eukaryotic Cell ◽  
Current Data ◽  
Cell Nuclei ◽  
Functional Roles ◽  
Translation Apparatus ◽  
Cell Stress Response

Components of the translation apparatus, including ribosomal proteins, have been found in cell nuclei in various organisms. Components of the translation apparatus are involved in various nuclear processes, particularly those associated with genome integrity control and the nuclear stages of gene expression, such as transcription, mRNA processing, and mRNA export. Components of the translation apparatus control intranuclear trafficking; the nuclear import and export of RNA and proteins; and regulate the activity, stability, and functional recruitment of nuclear proteins. The nuclear translocation of these components is often involved in the cell response to stimulation and stress, in addition to playing critical roles in oncogenesis and viral infection. Many components of the translation apparatus are moonlighting proteins, involved in integral cell stress response and coupling of gene expression subprocesses. Thus, this phenomenon represents a significant interest for both basic and applied molecular biology. Here, we provide an overview of the current data regarding the molecular functions of translation factors and ribosomal proteins in the cell nucleus.

scholarly journals High interaction valency ensures cohesion and persistence of a microtubule +TIP body at the plus-end of a single specialized microtubule in yeast

2021 ◽  
Author(s):  
Sandro Michael Meier ◽  
Ana-Maria Farcas ◽  
Anil Kumar ◽  
Mahdiye Ijavi ◽  
Robert Theofanis Bill ◽  
...  
Keyword(s):  
Eukaryotic Cell ◽  
Cytoplasmic Microtubule ◽  
Mechanical Coupling ◽  
Functional Roles ◽  
The Core ◽  
High Interaction ◽  
Actin Cables ◽  
Separation Of Proteins ◽  
Liquid Liquid Phase Separation

Microtubule plus-end tracking proteins (+TIPs) control microtubule specialization and are as such essential notably during eukaryotic cell division. Here, we investigated interactions and functions of the budding yeast Kar9 network consisting of the core +TIPs components Kar9 (functional homologue of APC, MACF, and SLAIN), Bim1 (orthologue of EB1), and Bik1 (orthologue of CLIP-170). Our data indicate that a redundant, multivalent web of interactions links the three +TIPs together to form a "Kar9 body" at the tip of a single cytoplasmic microtubule. They further suggest that this body is a liquid-like condensate, allowing it to persist on both growing and shrinking microtubule tips, and functions as a mechanical coupling device between microtubules and actin cables during mitosis. Our study underlines the power of dissecting the web of low-affinity interactions driving liquid-liquid phase separation of proteins in order to demonstrate the importance and establish the functional roles of condensation processes in vivo.

scholarly journals Comparison of the Microsatellite Distribution Patterns in the Genomes of Euarchontoglires at the Taxonomic Level

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuhao Song ◽  
Tingbang Yang ◽  
Xinyi Zhang ◽  
Ying Yuan ◽  
Xianghui Yan ◽  
...  
Keyword(s):  
Genome Size ◽  
Gc Content ◽  
Distribution Patterns ◽  
Functional Roles ◽  
Tree Shrews ◽  
Copy Numbers ◽  
Genome Wide ◽  
A Genome ◽  
Dinucleotide Motif ◽  
Evolution Of Mammals

Microsatellite or simple sequence repeat (SSR) instability within genes can induce genetic variation. The SSR signatures remain largely unknown in different clades within Euarchontoglires, one of the most successful mammalian radiations. Here, we conducted a genome-wide characterization of microsatellite distribution patterns at different taxonomic levels in 153 Euarchontoglires genomes. Our results showed that the abundance and density of the SSRs were significantly positively correlated with primate genome size, but no significant relationship with the genome size of rodents was found. Furthermore, a higher level of complexity for perfect SSR (P-SSR) attributes was observed in rodents than in primates. The most frequent type of P-SSR was the mononucleotide P-SSR in the genomes of primates, tree shrews, and colugos, while mononucleotide or dinucleotide motif types were dominant in the genomes of rodents and lagomorphs. Furthermore, (A)n was the most abundant motif in primate genomes, but (A)n, (AC)n, or (AG)n was the most abundant motif in rodent genomes which even varied within the same genus. The GC content and the repeat copy numbers of P-SSRs varied in different species when compared at different taxonomic levels, reflecting underlying differences in SSR mutation processes. Notably, the CDSs containing P-SSRs were categorized by functions and pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations, highlighting their roles in transcription regulation. Generally, this work will aid future studies of the functional roles of the taxonomic features of microsatellites during the evolution of mammals in Euarchontoglires.

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