scholarly journals Genome comparison implies the role of Wsm2 in membrane trafficking and protein degradation

2018 ◽  
Author(s):  
Guorong Zhang ◽  
Zhihua Hua
Keyword(s):  
Protein Degradation ◽  
Resistance Gene ◽  
Membrane Trafficking ◽  
Biological Function ◽  
Brachypodium Distachyon ◽  
Illegitimate Recombination ◽  
Grass Species ◽  
Wsmv Resistance ◽  
Chromosome 3B

Wheat streak mosaic virus (WSMV) causes streak mosaic disease in wheat (Triticum aestivum L.) and has been an important constraint limiting wheat production in many regions around the world. Wsm2 is the only resistance gene discovered in wheat genome and has been located in a short genomic region of its chromosome 3B. However, the sequence nature and the biological function of Wsm2 remain unknown due to the difficulty of genetic manipulation in wheat. In this study, we tested WSMV infectivity among wheat and its two closely related grass species, rice (Oryza sativa) and Brachypodium distachyon. Based on the phenotypic result and previous genomic studies, we developed a novel bioinformatics pipeline for interpreting a potential biological function of Wsm2 and its ancestor locus in wheat. In the WSMV resistance tests, we found that rice has a WMSV resistance gene while Brachypodium does not, which allowed us to hypothesize the presence of a Wsm2 ortholog in rice. Our OrthoMCL analysis of protein coding genes on wheat chromosome 3B and its syntenic chromosomes in rice and Brachypodium discovered 4,035 OrthoMCL groups as preliminary candidates of Wsm2 orthologs. Given that Wsm2 is likely duplicated through an intrachromosomal illegitimate recombination and that Wsm2 is dominant, we inferred that this new WSMV-resistance gene acquired an activation domain, lost an inhibition domain, or gained high expression compared to its ancestor locus. Through comparison, we identified that 67, 16, and 10 out of 4,035 OrthoMCL orthologous groups contain a rice member with 25% shorter or longer in length, or 10 fold more expression, respectively, than those from wheat and Brachypodium. Taken together, we predicted a total of 93 good candidates for a Wsm2 ancestor locus. All of these 93 candidates are not tightly linked with Wsm2, indicative of the role of illegitimate recombination in the birth of Wsm2. Further sequence analysis suggests that the protein products of Wsm2 may combat WSMV disease through a molecular mechanism involving protein degradation and/or membrane trafficking. The 93 putative Wsm2 ancestor loci discovered in this study could serve as good candidates for future genetic isolation of the true Wsm2 locus.

scholarly journals Genome comparison implies the role of Wsm2 in membrane trafficking and protein degradation

2018 ◽  
Author(s):  
Guorong Zhang ◽  
Zhihua Hua
Keyword(s):  
Protein Degradation ◽  
Resistance Gene ◽  
Membrane Trafficking ◽  
Biological Function ◽  
Brachypodium Distachyon ◽  
Illegitimate Recombination ◽  
Grass Species ◽  
Wsmv Resistance ◽  
Chromosome 3B

Wheat streak mosaic virus (WSMV) causes streak mosaic disease in wheat (Triticum aestivum L.) and has been an important constraint limiting wheat production in many regions around the world. Wsm2 is the only resistance gene discovered in wheat genome and has been located in a short genomic region of its chromosome 3B. However, the sequence nature and the biological function of Wsm2 remain unknown due to the difficulty of genetic manipulation in wheat. In this study, we tested WSMV infectivity among wheat and its two closely related grass species, rice (Oryza sativa) and Brachypodium distachyon. Based on the phenotypic result and previous genomic studies, we developed a novel bioinformatics pipeline for interpreting a potential biological function of Wsm2 and its ancestor locus in wheat. In the WSMV resistance tests, we found that rice has a WMSV resistance gene while Brachypodium does not, which allowed us to hypothesize the presence of a Wsm2 ortholog in rice. Our OrthoMCL analysis of protein coding genes on wheat chromosome 3B and its syntenic chromosomes in rice and Brachypodium discovered 4,035 OrthoMCL groups as preliminary candidates of Wsm2 orthologs. Given that Wsm2 is likely duplicated through an intrachromosomal illegitimate recombination and that Wsm2 is dominant, we inferred that this new WSMV-resistance gene acquired an activation domain, lost an inhibition domain, or gained high expression compared to its ancestor locus. Through comparison, we identified that 67, 16, and 10 out of 4,035 OrthoMCL orthologous groups contain a rice member with 25% shorter or longer in length, or 10 fold more expression, respectively, than those from wheat and Brachypodium. Taken together, we predicted a total of 93 good candidates for a Wsm2 ancestor locus. All of these 93 candidates are not tightly linked with Wsm2, indicative of the role of illegitimate recombination in the birth of Wsm2. Further sequence analysis suggests that the protein products of Wsm2 may combat WSMV disease through a molecular mechanism involving protein degradation and/or membrane trafficking. The 93 putative Wsm2 ancestor loci discovered in this study could serve as good candidates for future genetic isolation of the true Wsm2 locus.

scholarly journals Genome comparison implies the role of Wsm2 in membrane trafficking and protein degradation

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4678
Author(s):  
Guorong Zhang ◽  
Zhihua Hua
Keyword(s):  
Protein Degradation ◽  
Resistance Gene ◽  
Membrane Trafficking ◽  
Biological Function ◽  
Brachypodium Distachyon ◽  
Illegitimate Recombination ◽  
Grass Species ◽  
Wsmv Resistance ◽  
Chromosome 3B

Wheat streak mosaic virus (WSMV) causes streak mosaic disease in wheat (Triticum aestivum L.) and has been an important constraint limiting wheat production in many regions around the world. Wsm2 is the only resistance gene discovered in wheat genome and has been located in a short genomic region of its chromosome 3B. However, the sequence nature and the biological function of Wsm2 remain unknown due to the difficulty of genetic manipulation in wheat. In this study, we tested WSMV infectivity among wheat and its two closely related grass species, rice (Oryza sativa) and Brachypodium distachyon. Based on the phenotypic result and previous genomic studies, we developed a novel bioinformatics pipeline for interpreting a potential biological function of Wsm2 and its ancestor locus in wheat. In the WSMV resistance tests, we found that rice has a WMSV resistance gene while Brachypodium does not, which allowed us to hypothesize the presence of a Wsm2 ortholog in rice. Our OrthoMCL analysis of protein coding genes on wheat chromosome 3B and its syntenic chromosomes in rice and Brachypodium discovered 4,035 OrthoMCL groups as preliminary candidates of Wsm2 orthologs. Given that Wsm2 is likely duplicated through an intrachromosomal illegitimate recombination and that Wsm2 is dominant, we inferred that this new WSMV-resistance gene acquired an activation domain, lost an inhibition domain, or gained high expression compared to its ancestor locus. Through comparison, we identified that 67, 16, and 10 out of 4,035 OrthoMCL orthologous groups contain a rice member with 25% shorter or longer in length, or 10 fold more expression, respectively, than those from wheat and Brachypodium. Taken together, we predicted a total of 93 good candidates for a Wsm2 ancestor locus. All of these 93 candidates are not tightly linked with Wsm2, indicative of the role of illegitimate recombination in the birth of Wsm2. Further sequence analysis suggests that the protein products of Wsm2 may combat WSMV disease through a molecular mechanism involving protein degradation and/or membrane trafficking. The 93 putative Wsm2 ancestor loci discovered in this study could serve as good candidates for future genetic isolation of the true Wsm2 locus.

Aurora Kinase Inhibitors in Head and Neck Cancer

2018 ◽  
Vol 18 (3) ◽  
pp. 199-213
Author(s):  
Guangying Qi ◽  
Jing Liu ◽  
Sisi Mi ◽  
Takaaki Tsunematsu ◽  
Shengjian Jin ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Cancer Therapy ◽  
Kinase Inhibitors ◽  
Biological Function ◽  
Aurora Kinase ◽  
Aurora Kinases ◽  
Related Research ◽  
Chemotherapy Drugs ◽  
Aurora Kinase Inhibitors

Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. The study and application of these small-molecule inhibitors, especially in combination with chemotherapy drugs, represent a new direction in cancer treatment. This paper reviews studies on Aurora kinases from recent years, including studies of their biological function, their relationship with tumor progression, and their inhibitors.

scholarly journals Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

2021 ◽  
Vol 22 (9) ◽  
pp. 4425
Author(s):  
Alazne Arrazola Arrazola Sastre ◽  
Miriam Luque Luque Montoro ◽  
Hadriano M. Lacerda ◽  
Francisco Llavero ◽  
José L. Zugaza
Keyword(s):  
Membrane Trafficking ◽  
Neurodegenerative Disorders ◽  
Synaptic Vesicles ◽  
Intracellular Trafficking ◽  
Small Gtpases ◽  
Constant Flow ◽  
Parkinson’S Diseases ◽  
The Central Nervous System ◽  
Arf Gtpases

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

scholarly journals A Duplicated Copy of the Meiotic Gene ZIP4 Preserves up to 50% Pollen Viability and Grain Number in Polyploid Wheat

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 290
Author(s):  
Abdul Kader Alabdullah ◽  
Graham Moore ◽  
Azahara C. Martín
Keyword(s):  
Pollen Viability ◽  
Pollen Grains ◽  
Wheat Chromosome ◽  
Grain Number ◽  
Meiotic Gene ◽  
Chromosome 5B ◽  
Mutant Pollen ◽  
Female Gametogenesis ◽  
Chromosome 3B

Although most flowering plants are polyploid, little is known of how the meiotic process evolves after polyploidisation to stabilise and preserve fertility. On wheat polyploidisation, the major meiotic gene ZIP4 on chromosome 3B duplicated onto 5B and diverged (TaZIP4-B2). TaZIP4-B2 was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these meiotic stabilising effects could be important for preserving wheat fertility. A CRISPR Tazip4-B2 mutant was exploited to assess the contribution of the 5B duplicated ZIP4 copy in maintaining pollen viability and grain setting. Analysis demonstrated abnormalities in 56% of meiocytes in the Tazip4-B2 mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number occurred when Tazip4-B2 mutant plants were pollinated with the less viable Tazip4-B2 mutant pollen rather than with wild type pollen, suggesting that the stabilising effect of TaZIP4-B2 on meiosis has a greater consequence in subsequent male, rather than female gametogenesis. These studies reveal the extraordinary value of the wheat chromosome 5B TaZIP4-B2 duplication to agriculture and human nutrition. Future studies should further investigate the role of TaZIP4-B2 on female fertility and assess whether different TaZIP4-B2 alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change.

scholarly journals Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

scholarly journals 3,4-dehydro-L-proline Induces Programmed Cell Death in the Roots of Brachypodium distachyon

2021 ◽  
Vol 22 (14) ◽  
pp. 7548
Author(s):  
Artur Pinski ◽  
Alexander Betekhtin ◽  
Jolanta Kwasniewska ◽  
Lukasz Chajec ◽  
Elzbieta Wolny ◽  
...  
Keyword(s):  
Cell Death ◽  
Brachypodium Distachyon ◽  
Root Hairs ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cell Wall Proteins ◽  
Root Epidermis ◽  
Root Hair Development ◽  
Transmission Electron ◽  
Hair Development

As cell wall proteins, the hydroxyproline-rich glycoproteins (HRGPs) take part in plant growth and various developmental processes. To fulfil their functions, HRGPs, extensins (EXTs) in particular, undergo the hydroxylation of proline by the prolyl-4-hydroxylases. The activity of these enzymes can be inhibited with 3,4-dehydro-L-proline (3,4-DHP), which enables its application to reveal the functions of the HRGPs. Thus, to study the involvement of HRGPs in the development of root hairs and roots, we treated seedlings of Brachypodium distachyon with 250 µM, 500 µM, and 750 µM of 3,4-DHP. The histological observations showed that the root epidermis cells and the cortex cells beneath them ruptured. The immunostaining experiments using the JIM20 antibody, which recognizes the EXT epitopes, demonstrated the higher abundance of this epitope in the control compared to the treated samples. The transmission electron microscopy analyses revealed morphological and ultrastructural features that are typical for the vacuolar-type of cell death. Using the TUNEL test (terminal deoxynucleotidyl transferase dUTP nick end labelling), we showed an increase in the number of nuclei with damaged DNA in the roots that had been treated with 3,4-DHP compared to the control. Finally, an analysis of two metacaspases’ gene activity revealed an increase in their expression in the treated roots. Altogether, our results show that inhibiting the prolyl-4-hydroxylases with 3,4-DHP results in a vacuolar-type of cell death in roots, thereby highlighting the important role of HRGPs in root hair development and root growth.

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