| 1. |
- Agostinho, Ana, et al.
(författare)
-
High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation
- 2016
-
Ingår i: EMBO Reports. - Stockholm : Wiley-VCH Verlagsgesellschaft. - 1469-221X .- 1469-3178. ; 17:6, s. 901-913
-
Tidskriftsartikel (refereegranskat)abstract
- During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.
|
|
| 2. |
|
|
| 3. |
- Andréasson, Claes, et al.
(författare)
-
Mitochondria orchestrate proteostatic and metabolic stress responses
- 2019
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 20:10
-
Tidskriftsartikel (refereegranskat)abstract
- The eukaryotic cell is morphologically and functionally organized as an interconnected network of organelles that responds to stress and aging. Organelles communicate via dedicated signal transduction pathways and the transfer of information in form of metabolites and energy levels. Recent data suggest that the communication between organellar proteostasis systems is a cornerstone of cellular stress responses in eukaryotic cells. Here, we discuss the integration of proteostasis and energy fluxes in the regulation of cellular stress and aging. We emphasize the molecular architecture of the regulatory transcriptional pathways that both sense and control metabolism and proteostasis. A special focus is placed on mechanistic insights gained from the model organism budding yeast in signaling from mitochondria to the nucleus and how this shapes cellular fitness.
|
|
| 4. |
|
|
| 5. |
- Baud, Sébastien, et al.
(författare)
-
gurke and pasticcino3 mutants affected in embryo development are impaired in acetyl-CoA carboxylase.
- 2004
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 5:5
-
Tidskriftsartikel (refereegranskat)abstract
- Normal embryo development is required for correct seedling formation. The Arabidopsis gurke and pasticcino3 mutants were isolated from different developmental screens and the corresponding embryos exhibit severe defects in their apical region, affecting bilateral symmetry. We have recently identified lethal acc1 mutants affected in acetyl-CoA carboxylase 1 (ACCase 1) that display a similar embryo phenotype. A series of crosses showed that gk and pas3 are allelic to acc1 mutants, and direct sequencing of the ACC1 gene revealed point mutations in these new alleles. The isolation of leaky acc1 alleles demonstrated that ACCase 1 is essential for correct plant development and that mutations in ACCase affect cellular division in plants, as is the case in yeast. Interestingly, significant metabolic complementation of the mutant phenotype was obtained by exogenous supply of malonate, suggesting that the lack of cytosolic malonyl-CoA is likely to be the initial factor leading to abnormal development in the acc1 mutants.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Berger, Birgit S., et al.
(författare)
-
Parkinson's disease-associated receptor GPR37 is an ER chaperone for LRP6
- 2017
-
Ingår i: EMBO Reports. - : Wiley-Blackwell Publishing Inc.. - 1469-221X .- 1469-3178. ; 18:5, s. 712-725
-
Tidskriftsartikel (refereegranskat)abstract
- Wnt/beta-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky beta-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/beta-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.
|
|
| 9. |
- Berndtsson, Jens, et al.
(författare)
-
Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance
- 2020
-
Ingår i: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Respiratory chains are crucial for cellular energy conversion and consist of multi-subunit complexes that can assemble into supercomplexes. These structures have been intensively characterized in various organisms, but their physiological roles remain unclear. Here, we elucidate their function by leveraging a high-resolution structural model of yeast respiratory supercomplexes that allowed us to inhibit supercomplex formation by mutation of key residues in the interaction interface. Analyses of a mutant defective in supercomplex formation, which still contains fully functional individual complexes, show that the lack of supercomplex assembly delays the diffusion of cytochromec between the separated complexes, thus reducing electron transfer efficiency. Consequently, competitive cellular fitness is severely reduced in the absence of supercomplex formation and can be restored by overexpression of cytochromec. In sum, our results establish how respiratory supercomplexes increase the efficiency of cellular energy conversion, thereby providing an evolutionary advantage for aerobic organisms.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Cantù, Claudio, et al.
(författare)
-
A RING finger to wed TCF and β-catenin
- 2013
-
Ingår i: EMBO Reports. - : Wiley-Blackwell Publishing Inc.. - 1469-221X .- 1469-3178. ; 14:4, s. 295-296
-
Tidskriftsartikel (refereegranskat)
|
|
| 14. |
- Chen, Ziqing, et al.
(författare)
-
Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
- 2021
-
Ingår i: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 22:3
-
Tidskriftsartikel (refereegranskat)abstract
- Inadequate persistence of tumor-infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL-2 or IL-15 renders NK cells resistant to suppression by PGE2. Analyzing Cancer Genome Atlas (TCGA) data, we found that high NK cell gene signatures correlate with significantly improved overall survival in patients with high levels of the prostaglandin E synthase (PTGES). In vitro, IL-15, in contrast to IL-2, enriches for CD25(+)/CD54(+) NK cells with superior mTOR activity and increased expression of the cAMP hydrolyzing enzyme phosphodiesterase 4A (PDE4A). Consequently, this distinct population of NK cells maintains their function in the presence of PGE2 and shows an increased ability to infiltrate lung adenocarcinoma tumors in vitro and in vivo. Thus, strategies to enrich CD25(+)/CD54(+) NK cells for adoptive cell therapy should be considered.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Corkery, Dale, et al.
(författare)
-
An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes
- 2023
-
Ingår i: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 24:9
-
Tidskriftsartikel (refereegranskat)abstract
- Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms to maintain lysosomal integrity. Small membrane lesions are detected and repaired by the endosomal sorting complex required for transport (ESCRT) machinery while more extensively damaged lysosomes are cleared by a galectin-dependent selective macroautophagic pathway (lysophagy). In this study, we identify a novel role for the autophagosome-lysosome tethering factor, TECPR1, in lysosomal membrane repair. Lysosomal damage promotes TECPR1 recruitment to damaged membranes via its N-terminal dysferlin domain. This recruitment occurs upstream of galectin and precedes the induction of lysophagy. At the damaged membrane, TECPR1 forms an alternative E3-like conjugation complex with the ATG12-ATG5 conjugate to regulate ATG16L1-independent unconventional LC3 lipidation. Abolishment of LC3 lipidation via ATG16L1/TECPR1 double knockout impairs lysosomal recovery following damage.
|
|
| 18. |
- Cruz Alsina, Fernando, et al.
(författare)
-
Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
- 2016
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 17:4, s. 601-616
-
Tidskriftsartikel (refereegranskat)abstract
- Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development.
|
|
| 19. |
- Desnues, B, et al.
(författare)
-
Differential oxidative damage and expression of stress defence regulons in culturable and non-culturable Escherichia coli cells
- 2003
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 4:4, s. 400-404
-
Tidskriftsartikel (refereegranskat)abstract
- Potentially pathogenic bacteria, such as Escherichia coli and Vibrio cholerae, become non-culturable during stasis. The analysis of such cells has been hampered by difficulties in studying bacterial population heterogeneity. Using in situ detection of protein oxidation in single E. coli cells, and using a density-gradient centrifugation technique to separate culturable and non-culturable cells, we show that the proteins in non-culturable cells show increased and irreversible oxidative damage, which affects various bacterial compartments and proteins. The levels of expression of specific stress regulons are higher in non-culturable cells, confirming increased defects relating to oxidative damage and the occurrence of aberrant, such as by amino-acid misincorporation, proteins. Our data suggest that non-culturable cells are produced due to stochastic deterioration, rather than an adaptive programme, and pinpoint oxidation management as the 'Achilles heel' of these cells.
|
|
| 20. |
- Dorafshan, Eshagh, et al.
(författare)
-
Ash1 counteracts Polycomb repression independent of histone H3 lysine 36 methylation
- 2019
-
Ingår i: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 20:4
-
Tidskriftsartikel (refereegranskat)abstract
- Polycomb repression is critical for metazoan development. Equally important but less studied is the Trithorax system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. It was proposed that the Trithorax system acts via methylation of histone H3 at lysine 4 and lysine 36 (H3K36), thereby inhibiting histone methyltransferase activity of the Polycomb complexes. Here we test this hypothesis by asking whether the Trithorax group protein Ash1 requires H3K36 methylation to counteract Polycomb repression. We show that Ash1 is the only Drosophila H3K36-specific methyltransferase necessary to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments reveal no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which lysine 36 is replaced by arginine does not cause excessive repression of homeotic genes. Our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, needs revision.
|
|
| 21. |
- El Kharraz, S., et al.
(författare)
-
The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation
- 2021
-
Ingår i: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:12
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Evers, Kathinka, 1960-, et al.
(författare)
-
Proactive epigenesis and ethics - Response
- 2017
-
Ingår i: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 18:8, s. 1272-1272
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Fällman, Erik, et al.
(författare)
-
The unfolding of the P pili quaternary structure by stretching is reversible, not plastic
- 2005
-
Ingår i: EMBO Reports. - : Wiley-Blackwell. - 1469-221X .- 1469-3178. ; 6:1, s. 52-56
-
Tidskriftsartikel (refereegranskat)abstract
- P pili are protein filaments expressed by uropathogenic Escherichia coli that mediate binding to glycolipids on epithelial cell surfaces, which is a prerequisite for bacterial infection. When a bacterium, attached to a cell surface, is exposed to external forces, the pili, which are composed of ∼103PapA protein subunits arranged in a helical conformation, can elongate by unfolding to a linear conformation. This property is considered important for the ability of a bacterium to withstand shear forces caused by urine flow. It has hitherto been assumed that this elongation is plastic, thus constituting a permanent conformational deformation. We demonstrate, using optical tweezers, that this is not the case; the unfolding of the helical structure to a linear conformation is fully reversible. It is surmised that this reversibility helps the bacteria regain close contact to the host cells after exposure to significant shear forces, which is believed to facilitate their colonization.
|
|
| 31. |
- Garvanska, Dimitriya H., et al.
(författare)
-
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions
- 2024
-
Ingår i: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
-
Tidskriftsartikel (refereegranskat)abstract
- Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.
|
|
| 32. |
- Gomez-Gutierrez, Ruben, et al.
(författare)
-
Two structurally defined A & beta; polymorphs promote different pathological changes in susceptible mice
- 2023
-
Ingår i: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 24:8
-
Tidskriftsartikel (refereegranskat)abstract
- Misfolded A & beta; is involved in the progression of Alzheimers disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded A & beta; strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of A & beta;(40)/A & beta;(42) peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified A & beta; polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded A & beta; strains.
|
|
| 33. |
- Grenklo, Staffan, et al.
(författare)
-
A crucial role for profilin-actin in the intracellular motility of Listeria monocytogenes
- 2003
-
Ingår i: EMBO reports. - London : Nature Publishing Group. - 1469-221X .- 1469-3178. ; 4:5, s. 523-529
-
Tidskriftsartikel (refereegranskat)abstract
- We have examined the effect of covalently crosslinked profilin–actin (PxA), which closely matches the biochemical properties of ordinary profilin–actin and interferes with actin polymerization in vitro and in vivo, on Listeria monocytogenes motility. PxA caused a marked reduction in bacterial motility, which was accompanied by the detachment of bacterial tails. The effect of PxA was dependent on its binding to proline-rich sequences, as shown by the inability of PH133SxA, which cannot interact with such sequences, to impair Listeria motility. PxA did not alter the motility of a Listeria mutant that is unable to recruit Ena (Enabled)/VASP (vasodilator-stimulated phosphoprotein) proteins and profilin to its surface. Finally, PxA did not block the initiation of actin-tail formation, indicating that profilin–actin is only required for the elongation of actin filaments at the bacterial surface. Our findings provide further evidence that profilin–actin is important for actin-based processes, and show that it has a key function in Listeria motility.
|
|
| 34. |
- Guettou, Fatma, et al.
(författare)
-
Structural insights into substrate recognition in proton-dependent oligopeptide transporters
- 2013
-
Ingår i: EMBO Reports. - : Embo press. - 1469-221X .- 1469-3178. ; 14:9, s. 804-810
-
Tidskriftsartikel (refereegranskat)abstract
- Short-chain peptides are transported across membranes through promiscuous proton-dependent oligopeptide transporters (POTs)-a subfamily of the major facilitator superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the absorption of various drugs in the gut as well as transport to target cells. Here, we present a structure of an oligomeric POT transporter from Shewanella oneidensis (PepT(So2)), which was crystallized in the inward open conformation in complex with the peptidomimetic alafosfalin. All ligand-binding residues are highly conserved and the structural insights presented here are therefore likely to also apply to human POTs.
|
|
| 35. |
- Göndör, Anita, et al.
(författare)
-
Chromatin insulators and cohesins
- 2008
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 9:4, s. 327-329
-
Tidskriftsartikel (refereegranskat)
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Heilbronner, Goetz, et al.
(författare)
-
Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice
- 2013
-
Ingår i: EMBO Reports. - : NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND. - 1469-221X .- 1469-3178. ; 14:11, s. 1017-1022
-
Tidskriftsartikel (refereegranskat)abstract
- The polymorphic beta-amyloid lesions present in individuals with Alzheimers disease are collectively known as cerebral beta-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop beta-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and A beta 40/A beta 42 peptide ratio. To determine the nature of such beta-amyloid morphotypes, beta-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced beta-amyloid deposition with the morphological, conformational, and A beta 40/A beta 42 ratio characteristics of beta-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced b-amyloid deposits with the characteristics of beta-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced beta-amyloid deposits, although less prominent, and the induced deposits were similar to the beta-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated A beta in APP transgenic mice can be maintained by seeded conversion.
|
|
| 39. |
- Hill, Sandra Malmgren, 1987, et al.
(författare)
-
Restricted access: spatial sequestration of damaged proteins during stress and aging
- 2017
-
Ingår i: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 18:3, s. 377-391
-
Forskningsöversikt (refereegranskat)abstract
- The accumulation of damaged and aggregated proteins is a hallmark of aging and increased proteotoxic stress. To limit the toxicity of damaged and aggregated proteins and to ensure that the damage is not inherited by succeeding cell generations, a system of spatial quality control operates to sequester damaged/aggregated proteins into inclusions at specific protective sites. Such spatial sequestration and asymmetric segregation of damaged proteins have emerged as key processes required for cellular rejuvenation. In this review, we summarize findings on the nature of the different quality control sites identified in yeast, on genetic determinants required for spatial quality control, and on how aggregates are recognized depending on the stress generating them. We also briefly compare the yeast system to spatial quality control in other organisms. The data accumulated demonstrate that spatial quality control involves factors beyond the canonical quality control factors, such as chaperones and proteases, and opens up new venues in approaching how proteotoxicity might be mitigated, or delayed, upon aging.
|
|
| 40. |
|
|
| 41. |
- Huang, Tien-Sheng, et al.
(författare)
-
Functional inactivation of the SR family of splicing factors during a vaccinia virus infection
- 2002
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 3:11, s. 1088-1093
-
Tidskriftsartikel (refereegranskat)abstract
- SR proteins are essential splicing factors required for constitutive splicing and function as key regulators of alternative RNA splicing. We have shown that SR proteins purified from late adenovirus-infected cells (SR-Ad) are functionally inactivated as splicing enhancer or splicing repressor proteins by a virus-induced partial de-phosphorylation. Here, we show that SR proteins purified from late vaccinia-virus-infected cells (SR-VV) are also hypo-phosphorylated and functionally inactivated as splicing regulatory proteins. We further show that incubating SR-Ad proteins under conditions that restore the phospho-epitopes to the SR proteins results in the restoration of their activity as splicing enhancer and splicing repressor proteins. Interestingly, re-phosphorylation of SR-VV proteins only partially restored the splicing enhancer or splicing repressor phenotype to the SR proteins. Collectively, our results suggest that viral control of SR protein activity may be a common strategy used by DNA viruses to take control of the host cell RNA splicing machinery.
|
|
| 42. |
- Jakobsson, Hedvig E, et al.
(författare)
-
The composition of the gut microbiota shapes the colon mucus barrier.
- 2015
-
Ingår i: EMBO reports. - : EMBO. - 1469-3178 .- 1469-221X. ; 16, s. 164-177
-
Tidskriftsartikel (refereegranskat)abstract
- Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony. The thickness and growth of the colon mucus were similar in the two colonies. However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria-which is comparable to what we observed in free-living wild mice-whereas the other colony had an inner mucus layer penetrable to bacteria and beads. The different properties of the mucus depended on the microbiota, as they were transmissible by transfer of caecal microbiota to germ-free mice. Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus. Thus, our study shows that bacteria and their community structure affect mucus barrier properties in ways that can have implications for health and disease. It also highlights that genetically identical animals housed in the same facility can have rather distinct microbiotas and barrier structures.
|
|
| 43. |
|
|
| 44. |
- Johnsson, Anna, et al.
(författare)
-
HAT-HDAC interplay modulates global histone H3K14 acetylation in gene-coding regions during stress
- 2009
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 10:9, s. 1009-1014
-
Tidskriftsartikel (refereegranskat)abstract
- Histone acetylation and deacetylation are important for gene regulation. The histone acetyltransferase, Gcn5, is an activator of transcriptional initiation that is recruited to gene promoters. Here, we map genome-wide Gcn5 occupancy and histone H3K14ac at high resolution. Gcn5 is predominantly localized to coding regions of highly transcribed genes, where it collaborates antagonistically with the class-II histone deacetylase, Clr3, to modulate H3K14ac levels and transcriptional elongation. An interplay between Gcn5 and Clr3 is crucial for the regulation of many stress-response genes. Our findings suggest a new role for Gcn5 during transcriptional elongation, in addition to its known role in transcriptional initiation.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Kamerlin, Shina Caroline Lynn, 1981-
(författare)
-
Open Access, Plan S, and researchers' needs
- 2020
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 21:10
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Mandates with the aim to enforce Open Access publishing, such as Plan S, need to respect researchers' needs and should contribute to the broader goal of Open Science.
|
|
