scholarly journals Structure of the human FERRY Rab5 effector complex

2021 ◽  
Author(s):  
Dennis Quentin ◽  
Jan Schuhmacher ◽  
Bjoern Udo Klink ◽  
Janelle Lauer ◽  
Tanvir Shaikh ◽  
...  
Keyword(s):  
Regulation Of Gene Expression ◽  
Coiled Coil ◽  
Early Endosome ◽  
Coiled Coils ◽  
Mrna Transport ◽  
Long Distance ◽  
Temporal Regulation ◽  
Complex Core ◽  
Spatio Temporal ◽  
Insight Into

Long-range mRNA transport is crucial for the spatio-temporal regulation of gene expression, and its malfunction is linked to neurological disorders. The pentameric FERRY Rab5 effector complex is the molecular link between mRNA and the early endosome in mRNA intracellular distribution. Here, we determine the cryo-EM structure of the human FERRY complex, composed of Fy-1 to Fy-5. The structure reveals a clamp-like architecture, in which two arm-like appendages, each consisting of Fy-2 and a Fy-5 dimer, protrude from the central Fy-4 dimer. We demonstrate that the coiled-coil domains of Fy-2 are flexible and project into opposite directions from the FERRY complex core. While the C-terminal coiled-coil acts as binding region for Fy-1/3 and Rab5, both coiled-coils together with Fy-5 bind mRNA. Thus, Fy-2 serves as binding hub that connects not only all five complex subunits, but also mediates the binding to mRNA and to the early endosome via Rab5. The FERRY structure provides novel mechanistic insight into long-distance mRNA transport.

scholarly journals Two- and Three-Dimensional Tracking of MFA2 mRNA Molecules in Mating Yeast

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2151
Author(s):  
Polina Geva ◽  
Konstantin Komoshvili ◽  
Stella Liberman-Aronov
Keyword(s):  
Molecular Motors ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Three Dimensional ◽  
Movement Behavior ◽  
Mrna Transport ◽  
Yeast Saccharomyces Cerevisiae ◽  
Temporal Regulation ◽  
Spatio Temporal ◽  
Processing Body

Intracellular mRNA transport contributes to the spatio-temporal regulation of mRNA function and localized translation. In the budding yeast, Saccharomyces cerevisiae, asymmetric mRNA transport localizes ~30 specific mRNAs including those encoding polarity and secretion factors, to the bud tip. The underlying process involves RNA-binding proteins (RBPs), molecular motors, processing bodies (PBs), and the actin cytoskeleton. Recently, pheromone a-factor expression in mating yeast was discovered to depend on proper localization of its mRNA, MFA2 mRNAs in conjunction with PBs cluster at the shmoo tip to form “mating bodies”, from which a-factor is locally expressed. The mechanism ensuring the correct targeting of mRNA to the shmoo tip is poorly understood. Here we analyzed the kinetics and trajectories of MFA2 mRNA transport in living, alpha-factor treated yeast. Two- (2D) and three-dimensional (3D) analyses allowed us to reconstruct the granule tracks and estimate granule velocities. Tracking analysis of single MFA2 mRNA granules, labeled using a fluorescent aptamer system, demonstrated three types movement: vibrational, oscillatory and translocational. The mRNA granule transport was complex; a granule could change its movement behavior and composition during its journey to the shmoo. Processing body assembly and the actin-based motor, Myo4p, were involved in movement of MFA2 mRNA to the shmoo, but neither was required, indicating that multiple mechanisms for translocation were at play. Our visualization studies present a dynamic view of the localization mechanism in shmoo-bearing cells.

scholarly journals Separation of coiled-coil structures in lamin A/C is required for elongation of the filament

2020 ◽  
Author(s):  
Jinsook Ahn ◽  
Soyeon Jeong ◽  
So-mi Kang ◽  
Inseong Jo ◽  
Bum-Joon Park ◽  
...  
Keyword(s):  
Structural Transition ◽  
Coiled Coil ◽  
Binding Mode ◽  
Coiled Coils ◽  
Lamin A ◽  
Structural Elements ◽  
Mutant Proteins ◽  
Biochemical Effects ◽  
Insight Into

AbstractIntermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting of coil 1a, coil 1b, coil 2, and their flanking linkers. Recently, crystal structure of a long lamin A/C fragment was determined and showed detailed features of a tetrameric unit. The structure further suggested a new binding mode between tetramers, designated eA22, where a parallel overlap of coil 1a and coil 2 is the key interaction. In this study, we investigated the biochemical effects of genetic mutations causing human diseases, focusing on the eA22 interaction. The mutant proteins exhibited either weakened or augmented interactions between coil 1a and coil 2. The ensuing biochemical results indicated that the interaction requires the separation of the coiled-coils in N-terminal of coil 1a and C-terminal of coil 2, coupled with the structural transition in the central α-helical rod domain. This study provides insight into the role of coil 1a as a molecular regulator in elongation of the IF proteins.

scholarly journals Two- and three-dimensional tracking of MFA2 mRNA molecules in mating yeast

2020 ◽  
Author(s):  
Polina Geva ◽  
Konstantin Komoshvili ◽  
Stella Liberman-Aronov
Keyword(s):  
Molecular Motors ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Three Dimensional ◽  
Movement Behavior ◽  
Mrna Transport ◽  
Processing Bodies ◽  
Temporal Regulation ◽  
Spatio Temporal ◽  
Processing Body

AbstractIntracellular mRNA transport contributes to the spatio-temporal regulation of mRNA function and localized translation. In the budding yeast, Saccharomyces cerevisiae, asymmetric mRNA transport localizes ∼30 specific mRNAs including those encoding polarity and secretion factors, to the bud tip. The underlying process involves RNA binding proteins (RBPs), molecular motors, processing bodies (PBs), and the actin cytoskeleton. Recently, pheromone a-factor expression in mating yeast was discovered to depend upon proper localization of its mRNA, MFA2. MFA2 mRNAs in conjunction with PBs cluster at the shmoo tip to form “mating bodies”, from which a-factor is locally expressed. The mechanism ensuring the correct targeting of mRNA to the shmoo tip is poorly understood.Here we analyzed the kinetics and trajectories of MFA2 mRNA transport in living, alpha-factor treated yeast. Two-(2D) and three-dimensional (3D) analyses allowed us to reconstruct the granule tracks and estimate granule velocities. Tracking analysis of single MFA2 mRNA granules, labeled using a fluorescent aptamer system, demonstrated three types movement: vibrational, oscillatory and translocational. The mRNA granule transport was complex; a granule could change its movement behavior and composition during its journey to the shmoo. Processing body assembly and the actin-based motor, Myo4p, were involved in movement of MFA2 mRNA to the shmoo, but neither was required, indicating that multiple mechanisms for translocation were at play. Our visualization studies present a dynamic view of the localization mechanism in shmoo-bearing cells.

scholarly journals Confirmation of Bioinformatics Predictions of the Structural Domains in Honeybee Silk

Polymers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 776 ◽  
Author(s):  
Andrea Woodhead ◽  
Andrew Church ◽  
Trevor Rapson ◽  
Holly Trueman ◽  
Jeffrey Church ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Level Structure ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Advanced Materials ◽  
Structural Domain ◽  
Structural Elements ◽  
Film Properties ◽  
Structural Domains ◽  
Insight Into

Honeybee larvae produce a silk made up of proteins in predominantly a coiled coil molecular structure. These proteins can be produced in recombinant systems, making them desirable templates for the design of advanced materials. However, the atomic level structure of these proteins is proving difficult to determine: firstly, because coiled coils are difficult to crystalize; and secondly, fibrous proteins crystalize as fibres rather than as discrete protein units. In this study, we synthesised peptides from the central structural domain, as well as the N- and C-terminal domains, of the honeybee silk. We used circular dichroism spectroscopy, infrared spectroscopy, and molecular dynamics to investigate the folding behaviour of the central domain peptides. We found that they folded as predicted by bioinformatics analysis, giving the protein engineer confidence in bioinformatics predictions to guide the design of new functionality into these protein templates. These results, along with the infrared structural analysis of the N- and C-terminal domain peptides and the comparison of peptide film properties with those of the full-length AmelF3 protein, provided significant insight into the structural elements required for honeybee silk protein to form into stable materials.

scholarly journals Spatio-temporal regulation of gene expression defines subpopulations of epidermal stem cells

2020 ◽  
Vol 48 (6) ◽  
pp. 2839-2850
Author(s):  
Maneesha Aruketty ◽  
Svitlana Kurinna
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regulation Of Gene Expression ◽  
Stem Cell Markers ◽  
Epidermal Stem Cell ◽  
Epidermal Stem Cells ◽  
Cell Plasticity ◽  
Temporal Regulation ◽  
Spatio Temporal ◽  
High Degree

The search for epidermal stem cells has gained the momentum as they possess unique biological characteristics and a potential in regeneration therapies. Several transcription factors and miRNAs have been identified as epidermal stem cell markers. However, the separation of epidermal stem cells from their progeny remains challenging. The introduction of single-cell transcriptomics pointed to the high degree of heterogeneity in epidermal stem cells imbedded within subpopulations of keratinocytes. Pseudotime inference, RNA velocity, and cellular entropy further enhanced our knowledge of stem cells, allowing for the discovery of the epidermal stem cell plasticity. We explore the main findings that lead to the discovery of the plastic trait within the epidermal stem cells and the implications of cell plasticity in regenerative medicine.

scholarly journals Decoding transcription and microRNA-mediated translation control in Drosophila development

2010 ◽  
Vol 391 (7) ◽  
Author(s):  
Ulrike Gaul
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Binding Sites ◽  
Gene Network ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Translation Control ◽  
Temporal Regulation ◽  
Animal Development ◽  
Spatio Temporal

Abstract The spatio-temporal regulation of gene expression lies at the heart of animal development. In this article we present an overview of our recent work to apply systems biological approaches to the study of transcription and microRNA-mediated translation control in Drosophila development. We have identified many new cis-regulatory elements within the segmentation gene network, a transcriptional hierarchy governing pattern formation along the antero-posterior axis of the embryo, and developed a novel thermodynamic model to predict their expression. A similar thermodynamic approach that takes into account the secondary structure of the target mRNA significantly improves the prediction of microRNA binding sites.

scholarly journals Separation of Coiled-Coil Structures in Lamin A/C Is Required for the Elongation of the Filament

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 55
Author(s):  
Jinsook Ahn ◽  
Soyeon Jeong ◽  
So-Mi Kang ◽  
Inseong Jo ◽  
Bum-Joon Park ◽  
...  
Keyword(s):  
Structural Transition ◽  
Coiled Coil ◽  
Binding Mode ◽  
Coiled Coils ◽  
Lamin A ◽  
Structural Elements ◽  
Mutant Proteins ◽  
Biochemical Effects ◽  
Insight Into

Intermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting of coil 1a, coil 1b, coil 2, and their flanking linkers. Recently, the crystal structure of a long lamin A/C fragment was determined and showed detailed features of a tetrameric unit. The structure further suggested a new binding mode between tetramers, designated eA22, where a parallel overlap of coil 1a and coil 2 is the critical interaction. This study investigated the biochemical effects of genetic mutations causing human diseases, focusing on the eA22 interaction. The mutant proteins exhibited either weakened or augmented interactions between coil 1a and coil 2. The ensuing biochemical results indicated that the interaction requires the separation of the coiled-coils in the N-terminal of coil 1a and the C-terminal of coil 2, coupled with the structural transition in the central α-helical rod domain. This study provides insight into the role of coil 1a as a molecular regulator in the elongation of IF proteins.

scholarly journals Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zi Wang ◽  
Pan Wang ◽  
Yanan Li ◽  
Hongling Peng ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Hematological Malignancies ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hematologic Disorders ◽  
Cell Lineages ◽  
Stage Of Development ◽  
Transcription Complexes ◽  
Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

scholarly journals Geomagnetic imprinting predicts spatio-temporal variation in homing migration of pink and sockeye salmon

2014 ◽  
Vol 11 (99) ◽  
pp. 20140542 ◽  
Author(s):  
Nathan F. Putman ◽  
Erica S. Jenkins ◽  
Catherine G. J. Michielsens ◽  
David L. G. Noakes
Keyword(s):  
Magnetic Field ◽  
Temporal Variation ◽  
Ocean Circulation ◽  
Sockeye Salmon ◽  
Movement Patterns ◽  
Oncorhynchus Gorbuscha ◽  
Migration Routes ◽  
Long Distance ◽  
Spatio Temporal ◽  
Olfactory Imprinting

Animals navigate using a variety of sensory cues, but how each is weighted during different phases of movement (e.g. dispersal, foraging, homing) is controversial. Here, we examine the geomagnetic and olfactory imprinting hypotheses of natal homing with datasets that recorded variation in the migratory routes of sockeye ( Oncorhynchus nerka ) and pink ( Oncorhynchus gorbuscha ) salmon returning from the Pacific Ocean to the Fraser River, British Columbia. Drift of the magnetic field (i.e. geomagnetic imprinting) uniquely accounted for 23.2% and 44.0% of the variation in migration routes for sockeye and pink salmon, respectively. Ocean circulation (i.e. olfactory imprinting) predicted 6.1% and 0.1% of the variation in sockeye and pink migration routes, respectively. Sea surface temperature (a variable influencing salmon distribution but not navigation, directly) accounted for 13.0% of the variation in sockeye migration but was unrelated to pink migration. These findings suggest that geomagnetic navigation plays an important role in long-distance homing in salmon and that consideration of navigation mechanisms can aid in the management of migratory fishes by better predicting movement patterns. Finally, given the diversity of animals that use the Earth's magnetic field for navigation, geomagnetic drift may provide a unifying explanation for spatio-temporal variation in the movement patterns of many species.

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