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Protein-RNA recognition is essential for gene expression and its regulation, which is indispensable for the survival of the living organism at one hand, on the other hand, misregulation of this recognition may lead to their extinction. Polymorphic conformation of both the interacting partners is a characteristic feature of such molecular recognition that promotes the assembly. Many RNA binding proteins (RBP) or regions in them are found to be intrinsically disordered, and this property helps them to play a central role in the regulatory processes. Sequence composition and the length of the flexible linkers between RNA binding domains in RBPs are crucial in making significant contacts with its partner RNA. Polymorphic conformations of RBPs can provide thermodynamic advantage to its binding partner while acting as a chaperone. Prolonged extensions of the disordered regions in RBPs also contribute to the stability of the large cellular machines including ribosome and viral assemblies. The involvement of these disordered regions in most of the significant cellular processes makes RBPs highly associated with various human diseases that arise due to their misregulation.

Protein–RNA recognition often induces conformational changes in binding partners. Consequently, the solvent accessible surface area (SASA) buried in contact estimated from the co-crystal structures may differ from that calculated using their unbound forms. To evaluate the change in accessibility upon binding, we compare SASA of 126 protein-RNA complexes between bound and unbound forms. We observe, in majority of cases the interface of both the binding partners gain accessibility upon binding, which is often associated with either large domain movements or secondary structural transitions in RNA-binding proteins (RBPs), and binding-induced conformational changes in RNAs. At the non-interface region, majority of RNAs lose accessibility upon binding, however, no such preference is observed for RBPs. Side chains of RBPs have major contribution in change in accessibility. In case of flexible binding, we find a moderate correlation between the binding free energy and change in accessibility at the interface. Finally, we introduce a parameter, the ratio of gain to loss of accessibility upon binding, which can be used to identify the native solution among the flexible docking models. Our findings provide fundamental insights into the relationship between flexibility and solvent accessibility, and advance our understanding on binding induced folding in protein-RNA recognition.

The DREB genes code for important plant transcription factors involved in the abiotic stress response and signal transduction. Characterization of DREB genes and development of functional markers for effective alleles is important for marker-assisted selection in foxtail millet. Here the characterization of a cDNA (SiDREB2) encoding a putative dehydration-responsive element-binding protein 2 from foxtail millet and the development of an allele-specific marker (ASM) for dehydration tolerance is reported. A cDNA clone (GenBank accession no. GT090998) coding for a putative DREB2 protein was isolated as a differentially expressed gene from a 6 h dehydration stress SSH library. A 5' RACE (rapid amplification of cDNA ends) was carried out to obtain the full-length cDNA, and sequence analysis showed that SiDREB2 encoded a polypeptide of 234 amino acids with a predicted mol. wt of 25.72 kDa and a theoretical pl of 5.14. A theoretical model of the tertiary structure shows that it has a highly conserved GCC-box-binding N-terminal domain, and an acidic C-terminus that acts as an activation domain for transcription. Based on its similarity to AP2 domains, SiDREB2 was classified into the A-2 subgroup of the DREB subfamily. Quantitative real-time PCR analysis showed significant up-regulation of SiDREB2 by dehydration (polyethylene glycol) and salinity (NaCl), while its expression was less affected by other stresses. A synonymous single nucleotide polymorphism (SNP) associated with dehydration tolerance was detected at the 558th base pair (an A/G transition) in the SiDREB2 gene in a core set of 45 foxtail millet accessions used. Based on the identified SNP, three primers were designed to develop an ASM for dehydration tolerance. The ASM produced a 261 bp fragment in all the tolerant accessions and produced no amplification in the sensitive accessions. The use of this ASM might be faster, cheaper, and more reproducible than other SNP genotyping methods, and thus will enable marker-aided breeding of foxtail millet for dehydration tolerance.

Monkeypox virus (mpox virus) outbreak has rapidly spread to 82 non-endemic countries. Although it primarily causes skin lesions, secondary complications and high mortality (1–10%) in vulnerable populations have made it an emerging threat. Since there is no specific vaccine/antiviral, it is desirable to repurpose existing drugs against mpox virus. With little knowledge about the lifecycle of mpox virus, identifying potential inhibitors is a challenge. Nevertheless, the available genomes of mpox virus in public databases represent a goldmine of untapped possibilities to identify druggable targets for the structure-based identification of inhibitors. Leveraging this resource, we combined genomics and subtractive proteomics to identify highly druggable core proteins of mpox virus. This was followed by virtual screening to identify inhibitors with affinities for multiple targets. 125 publicly available genomes of mpox virus were mined to identify 69 highly conserved proteins. These proteins were then curated manually. These curated proteins were funnelled through a subtractive proteomics pipeline to identify 4 highly druggable, non-host homologous targets namely; A20R, I7L, Top1B and VETFS. High-throughput virtual screening of 5893 highly curated approved/investigational drugs led to the identification of common as well as unique potential inhibitors with high binding affinities. The common inhibitors, i.e., batefenterol, burixafor and eluxadoline were further validated by molecular dynamics simulation to identify their best potential binding modes. The affinity of these inhibitors suggests their repurposing potential. This work can encourage further experimental validation for possible therapeutic management of mpox. [Display omitted] •I7L, Top1B, VETFS and A20R were identified as critical therapeutic targets of mpox virus by using subtractive proteomics.•High-throughput virtual screening of FDA approved/investigational drugs identified the promising hits against these targets.•Batefenterol, burixafor and eluxadoline were found to have high affinity for multiple targets.•MD simulation revealed favourable interactions and stability of these drugs with I7L, Top1B and VETFS.•Molecular docking, MD Simulation and MMGBSA analysis suggest the suitability of these drugs for repurposing against mpox.

Background Pancreatic cancer, a highly lethal malignancy, is influenced by complex lncRNA-mediated gene expression. This study identified CASC19 as a significantly overexpressed lncRNA with high oncogenic potential in pancreatic cancer, aiming to uncover its molecular mechanism in tumor progression. Methods CASC19 expression was evaluated by qRT-PCR. Proliferation abilities of CASC19 were evaluated by MTT assay, cell cycle and apoptosis assay, upon CASC19 overexpression and knockdown. Whereas its metastatic potential was evaluated by wound healing, migration and invasion assay. The effect of CASC19 on cellular transcriptome was also examined by RNA sequencing after CASC19 overexpression and silencing. Subcellular localization of the lncRNA was examined by subcellular fractionation followed by qRT-PCR. To find out the molecular mechanism of lncRNA function, RNA-pull down, mass-spectrometry, immunoprecipitation, protein stability and ubiquitination assays were done. Results High CASC19 expression was found in pancreatic tumor tissues and multiple pancreatic cancer cell lines. In-vitro loss and gain-of-function experiments showed that CASC19 is an oncogenic lncRNA promoting proliferation and metastasis of pancreatic cancer, while inhibiting apoptosis. CASC19 was also found to regulate global transcriptome of pancreatic cancer cells, affecting pathways like TGF-β signaling pathway, β-Catenin-TCF complex assembly, etc. CASC19 was localized to nucleus of pancreatic cancer cells and was identified to interact with PSPC1, a metastatic reprogramming protein. The interaction results in prevention of ubiquitin-mediated degradation of PSPC1. Increased availability of PSPC1, in turn, potentiates nuclear retention of β-Catenin which ultimately triggers pancreatic cancer progression. Conclusion Our findings elaborate the mechanism of CASC19 mediated tumorigenesis in pancreatic cancer, highlighting the role of PSPC1 in the process. Targeting CASC19/PSPC1/β-Catenin axis could be a novel approach to impede the progression of the disease.

Background Non-coding RNAs (ncRNAs) are important players in the post transcriptional regulation of gene expression (PTGR). On one hand, microRNAs (miRNAs) are an abundant class of small ncRNAs (~22nt long) that negatively regulate gene expression at the levels of messenger RNAs stability and translation inhibition, on the other hand, long ncRNAs (lncRNAs) are a large and diverse class of transcribed non-protein coding RNA molecules (> 200nt) that play both up-regulatory as well as down-regulatory roles at the transcriptional level. Cajanus cajan, a leguminosae pulse crop grown in tropical and subtropical areas of the world, is a source of high value protein to vegetarians or very poor populations globally. Hence, genome-wide identification of miRNAs and lncRNAs in C. cajan is extremely important to understand their role in PTGR with a possible implication to generate improve variety of crops. Results We have identified 616 mature miRNAs in C. cajan belonging to 118 families, of which 578 are novel and not reported in MirBase21. A total of 1373 target sequences were identified for 180 miRNAs. Of these, 298 targets were characterized at the protein level. Besides, we have also predicted 3919 lncRNAs. Additionally, we have identified 87 of the predicted lncRNAs to be targeted by 66 miRNAs. Conclusions miRNA and lncRNAs in plants are known to control a variety of traits including yield, quality and stress tolerance. Owing to its agricultural importance and medicinal value , the identified miRNA, lncRNA and their targets in C. cajan may be useful for genome editing to improve better quality crop. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of C. cajan agricultural traits.

This case report describes a severe birth defect called anencephaly in a fetus at 18 weeks of pregnancy. Anencephaly occurs when the upper part of the baby's brain and skull do not form correctly. This condition is usually detected earlier in pregnancy, often in the first three months. However, this case was discovered at 18 weeks, highlighting the need for careful monitoring throughout pregnancy. The unique aspect of this case is that most pregnancies with anencephaly do not progress this far. This later diagnosis provides important information about the different ways the condition can develop. By studying cases like this, healthcare providers can improve prenatal care and potentially detect such defects earlier, even in the later stages of pregnancy. Overall, this report emphasizes the importance of continuous monitoring during pregnancy and offers insights that could lead to better diagnosis, care, and support for families facing similar situations.

The plant-specific NAC (NAM, ATAF, and CUC) transcription factors have diverse role in development and stress regulation. A transcript encoding NAC protein, termed SiNAC was identified from a salt stress subtractive cDNA library of S. italica seedling (Puranik et al., J Plant Physiol 168:280–287, 2011). This single/low copy gene containing four exons and four introns within the genomic-sequence encoded a protein of 462 amino acids. Structural analysis revealed that highly divergent C terminus contains a transmembrane domain. The NAC domain consisted of a twisted antiparallel beta-sheet packing against N terminal alpha helix on one side and a shorter helix on the other side. The domain was predicted to homodimerize and control DNA-binding specificity. The physicochemical features of the SiNAC homodimer interface justified the dimeric form of the predicted model. A 1539 bp fragment upstream to the start codon of SiNAC gene was cloned and in silico analysis revealed several putative cis-acting regulatory elements within the promoter sequence. Transactivation analysis indicated that SiNAC activated expression of reporter gene and the activation domain lied at the C terminal. The SiNAC:GFP was detected in the nucleus and cytoplasm while SiNAC ΔC1−158:GFP was nuclear localized in onion epidermal cells. SiNAC transcripts mostly accumulated in young spikes and were strongly induced by dehydration, salinity, ethephon, and methyl jasmonate. These results suggest that SiNAC encodes a membrane associated NAC-domain protein that may function as a transcriptional activator in response to stress and developmental regulation in plants.

This study investigates the effects of transportation, specifically public transit, the built environment, and sociodemographic factors on community quality of life (QOL) and individuals’ overall life satisfaction (OLS) in the United States. Using data from the 2017 National Community Livability Survey (NCLS), which includes responses from 994 adults across all 50 states, structural equation modeling (SEM) was applied to examine four latent constructs: the built environment, access to amenities, transportation quality, and support for transit funding. Additional observed variables included perceived importance of public transit, public transit need, ease of travel, and key sociodemographic indicators. Results show that the built environment and transportation quality significantly enhance community QOL but do not have a direct effect on individual OLS. In contrast, support for transit funding has a significant positive effect on individual OLS but not on community QOL. Public transit and walking access to amenities such as parks and recreation facilities, grocery stores, healthcare services, etc., improve both the built environment’s perceptions and community QOL. Interestingly, the perceived importance of public transit negatively influences community QOL, while perceived transit need negatively impacts individual OLS. Ease of travel is the only factor with a significant positive effect on both outcomes. Sociodemographic factors such as gender, age, income, health, education, and race are also found to significantly influence individual life satisfaction. These findings suggest that enhancing perceptions of the built environment, improving transportation quality—particularly public and active transit—and ensuring ease of travel can contribute to improved quality of life. Policies that integrate transportation planning with broader livability and well-being goals may offer more inclusive benefits at both the community and individual levels.

Non-coding RNAs (ncRNAs) are major players in the regulation of gene expression. This study analyses seven classes of ncRNAs in plants using sequence and secondary structure-based RNA folding measures. We observe distinct regions in the distribution of AU content along with overlapping regions for different ncRNA classes. Additionally, we find similar averages for minimum folding energy index across various ncRNAs classes except for pre-miRNAs and lncRNAs. Various RNA folding measures show similar trends among the different ncRNA classes except for pre-miRNAs and lncRNAs. We observe different k-mer repeat signatures of length three among various ncRNA classes. However, in pre-miRs and lncRNAs, a diffuse pattern of k-mers is observed. Using these attributes, we train eight different classifiers to discriminate various ncRNA classes in plants. Support vector machines employing radial basis function show the highest accuracy (average F1 of ~96%) in discriminating ncRNAs, and the classifier is implemented as a web server, NCodR.