Targeting BRF2: insights from in silico screening and molecular dynamic simulations.

The Transcription factor II B (TFIIB)­related factor 2 (BRF2) containing TFIIIB complex recruits RNA polymerase III multi-subunit complex to selective gene promoters that altogether are responsible for synthesizing a variety of small non-coding RNAs, including a special type of selenocysteine tRNA (tRNASec), micro-RNA (miRNA), and other regulatory RNAs. BRF2 has been identified as a potential oncogene that promotes cancer cell survival under oxidative stress through its genetic activation. The structure of the BRF2 protein was modeled using the Robetta server, refined, and validated using the Ramachandran plot. A virtual approach utilizing molecular docking was used to screen a natural compound library to determine potential compounds that can interact with the molecular pin motif of the BRF2 protein using Maestro (Schrodinger). Subsequent molecular dynamics simulation studies of the top four ligands that exhibited low glide scores were performed using GROMACS. The findings derived from the simulations, in conjunction with the exploration of hydrogen bonding patterns, evaluation of the free energy landscape, and thorough analysis of residue decomposition, collectively converged to emphasize the robust interaction characteristics exhibited by Ligand 366 (Deacetyl lanatoside C) and ligand 336 (Neogitogenin)-with the BRF2 protein. These natural compounds may be potential inhibitors of BRF2, which could modulate the regulation of selenoprotein synthesis in cancer cells. Targeting BRF2 using these promising compounds may offer a new therapeutic approach to sensitize cancer cells to ferroptosis and apoptosis.Communicated by Ramaswamy H. Sarma.

In silico identification of a promising inhibitor of Fusarium oxysporum f. sp. Lycopersici, Secreted in Xylem 1 protein.

Fusarium oxysporum f. sp. Lycopersici (FOL) is a soilborne pathogen that infects tomato plants and inflicts severe damage, resulting in heavy yield losses worldwide, causing Fusarium wilt disease. FOL encodes several pathogenicity factors necessary for colonizing and invading the host plants. Secreted in Xylem (SIX), a pathogenicity factor, is a small cysteine-rich fungal protein found in the xylem sap of FOL-infected tomato plants, which plays a major role in determining host specificity and in contributing to pathogenicity/virulence. However, the structure of SIX1 has not been modeled yet. Therefore, this study aimed to elucidate the structure of SIX1 by comparative modeling using Robetta server. The best possible structures obtained were then refined, validated, and utilized for subsequent analysis. An antifungal library comprising 16,824 compounds was screened to determine small molecules that can interact with SIX1. Five antifungal compounds were identified from the library. Further analyses revealed that, of the five ligands, 4-[(2-(3-methoxyphenoxy)acetyl)amino] benzamide exhibited the capacity to stably interact with SIX1. This shows that 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide can be used as a potential candidate in the prevention of FOL infection. In summary, small-molecule inhibitors such as 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide could be highly effective in combating FOL infection, along with biocontrol methods and strategies that use transgenic plants overexpressing resistance genes.

Selenium: a potent regulator of ferroptosis and biomass production.

Emerging evidence supports the notion that selenium (Se) plays a beneficial role in plant development for modern crop production and is considered an essential micronutrient and the predominant source of plants. However, the essential role of selenium in plant metabolism remains unclear. When used in moderate concentrations, selenium promotes plant physiological processes such as enhancing plant growth, increasing antioxidant capacity, reducing reactive oxygen species and lipid peroxidation and offering stress resistance by preventing ferroptosis cell death. Ferroptosis, a recently discovered mechanism of regulated cell death (RCD) with unique features such as iron-dependant accumulation of lipid peroxides, is distinctly different from other known forms of cell death. Glutathione peroxidase (GPX) activity plays a significant role in scavenging the toxic by-products of lipid peroxidation in plants. A low level of GPX activity in plants causes high oxidative stress, which leads to ferroptosis. An integrated view of ferroptosis and selenium in plants and the selenium-mediated nanofertilizers (SeNPs) have been discussed in more recent studies. For instance, selenium supplementation enhanced GPX4 expression and increased TFH cell (Follicular helper T) numbers and the gene transcriptional program, which prevent lipid peroxidase and protect cells from ferroptosis. However, though ferroptosis in plants is similar to that in animals, only few studies have focused on plant-specific ferroptosis; the research on ferroptosis in plants is still in its infancy. Understanding the implication of selenium with relevance to ferroptosis is indispensable for plant bioresource technology. In this review, we hypothesize that blocking ferroptosis cell death improves plant immunity and protects plants from abiotic and biotic stresses. We also examine how SeNPs can be the basis for emerging unconventional and advanced technologies for algae/bamboo biomass production. For instance, algae treated with SeNPs accumulate high lipid profile in algal cells that could thence be used for biodiesel production. We also suggest that further studies in the field of SeNPs are essential for the successful application of this technology for the large-scale production of plant biomass.

Topologies of N6 -adenosine methylation (m6 A) in land plant mitochondria and their putative effects on organellar gene expression.

Mitochondria serve as major sites of ATP production and play key roles in many other metabolic processes that are critical to the cell. As relicts of an ancient bacterial endosymbiont, mitochondria contain their own hereditary material (i.e. mtDNA, or mitogenome) and a machinery for protein biosynthesis. The expression of the mtDNA in plants is complex, particularly at the post-transcriptional level. Following transcription, the polycistronic pre-RNAs undergo extensive modifications, including trimming, splicing and editing, before being translated by organellar ribosomes. Our study focuses on N6 -methylation of adenosine ribonucleotides (m6 A-RNA) in plant mitochondria. m6 A is a prevalent modification in nuclear-encoded mRNAs. The biological significance of this dynamic modification is under investigation, but it is widely accepted that m6 A mediates structural switches that affect RNA stability and/or activity. Using m6 A-pulldown/RNA-seq (m6 A-RIP-seq) assays of Arabidopsis and cauliflower mitochondria, we provide information on the m6 A-RNA landscapes in Arabidopsis thaliana and Brassica oleracea mitochondria. The results show that m6 A targets different types of mitochondrial transcripts, including known genes, mtORFs, as well as non-coding (transcribed intergenic) RNA species. While ncRNAs undergo multiple m6 A modifications, N6 -methylation of adenosine residues with mRNAs seem preferably positioned near start codons and may modulate their translatability.