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rabindra.tharu.np@gmail.com
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webTWAS 2.0: update platform for identifying complex disease susceptibility genes through transcriptome-wide association study
Transcriptome-wide association study (TWAS) has successfully identified numerous complex disease susceptibility genes in the post-genome-wide association study (GWAS) era. Over the past 3 years, the focus of TWAS algorithms has shifted from merely identifying associations to understanding how single nucleotide polymorphisms (SNPs) regulate gene expression, with a growing emphasis on incorporating fine-mapping techniques. Additionally, the rapid increase…
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rabindra.tharu.np@gmail.com
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KEGG: biological systems database as a model of the real world
KEGG (https://www.kegg.jp/) is a database resource for representation and analysis of biological systems. Pathway maps are the primary dataset in KEGG representing systemic functions of the cell and the organism in terms of molecular interaction and reaction networks. The KEGG Orthology (KO) system is a mechanism for linking genes and proteins to pathway maps and…
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rabindra.tharu.np@gmail.com
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Various plasmid strategies limit the effect of bacterial restriction-modification systems against conjugation
In bacteria, genes conferring antibiotic resistance are mostly carried on conjugative plasmids, mobile genetic elements that spread horizontally between bacterial hosts. Bacteria carry defence systems that defend them against genetic parasites, but how effective these are against plasmid conjugation is poorly understood. Here, we study to what extent restriction-modification (RM) systems-by far the most prevalent…
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rabindra.tharu.np@gmail.com
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Massively parallel binding assay (MPBA) reveals limited transcription factor binding cooperativity, challenging models of specificity
DNA-binding domains (DBDs) within transcription factors (TFs) recognize short sequence motifs that are highly abundant in genomes. In vivo, TFs bind only a small subset of motif occurrences, which is often attributed to the cooperative binding of interacting TFs at proximal motifs. However, large-scale testing of this model is still lacking. Here, we describe a…
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rabindra.tharu.np@gmail.com
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The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state
The basic zippers (bZIPs) are one of two large eukaryotic families of transcription factors whose DNA binding domains are disordered in isolation but fold into stable α-helices upon target DNA binding. Here, we systematically disrupt pre-existing helical propensity within the DNA binding region of the homodimeric bZIP domain of cAMP-response element binding protein (CREB) using…
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rabindra.tharu.np@gmail.com
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DORQ-seq: high-throughput quantification of femtomol tRNA pools by combination of cDNA hybridization and Deep sequencing
Due to its high modification content tRNAs are notoriously hard to quantify by reverse transcription and RNAseq. Bypassing numerous biases resulting from concatenation of enzymatic treatments, we here report a hybrid approach that harnesses the advantages of hybridization-based and deep sequencing-based approaches. The method renders obsolete any RNAseq related workarounds and correction factors that affect…
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rabindra.tharu.np@gmail.com
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Structural basis for the concerted antiphage activity in the SIR2-HerA system
Recently, a novel two-gene bacterial defense system against phages, encoding a SIR2 NADase and a HerA ATPase/helicase, has been identified. However, the molecular mechanism of the bacterial SIR2-HerA immune system remains unclear. Here, we determine the cryo-EM structures of SIR2, HerA and their complex from Paenibacillus sp. 453MF in different functional states. The SIR2 proteins…
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rabindra.tharu.np@gmail.com
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The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation
During mammalian embryogenesis, both the 5-cytosine DNA methylation (5meC) landscape and three dimensional (3D) chromatin architecture are profoundly remodeled during a process known as ‘epigenetic reprogramming.’ An understudied aspect of epigenetic reprogramming is how the 5meC flux, per se, affects the 3D genome. This is pertinent given the 5meC-sensitivity of DNA binding for a key…
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rabindra.tharu.np@gmail.com
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Methods for constructing and evaluating consensus genomic interval sets
The amount of genomic region data continues to increase. Integrating across diverse genomic region sets requires consensus regions, which enable comparing regions across experiments, but also by necessity lose precision in region definitions. We require methods to assess this loss of precision and build optimal consensus region sets. Here, we introduce the concept of flexible…
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rabindra.tharu.np@gmail.com
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RudS: bacterial desulfidase responsible for tRNA 4-thiouridine de-modification
In this study, we present an extensive analysis of a widespread group of bacterial tRNA de-modifying enzymes, dubbed RudS, which consist of a TudS desulfidase fused to a Domain of Unknown Function 1722 (DUF1722). RudS enzymes exhibit specific de-modification activity towards the 4-thiouridine modification (s4U) in tRNA molecules, as indicated by our experimental findings. The heterologous…
