Biology subjects

Qureshi, H.

Publications and source records attributed to Qureshi, H..

4 recordsLinked to original sources

bioRxiv2026

The specific interface for selenocysteine-decoding tRNA in HIV-1 Gag MAdomain regulates progeny virion infectivity

Localization of HIV-1 particle assembly at the plasma membrane (PM) is mediated by the HIV-1 Gag matrix (MA) domain. Competing binding of PM acidic phospholipids and cellular tRNAs to MA-highly basic region (MA-HBR) likely regulate the PM-specific binding of Gag; however, the specificity of the MA-tRNA interaction and its role in viral replication remain poorly understood. Here, using a modified crosslinking-immunoprecipitation (CLIP)-sequencing workflow for identifying MA-bound tRNAs, we determined that most MA-bound tRNAs were also abundantly present in cells. However, selenocysteine-tRNA (SeCTCA) is overrepresented among Gag-bound tRNAs despite its paucity. The binding of SeCTCA to Gag is entirely dependent on MA-HBR, whereas non-SeCTCA tRNAs can bind Gag through both MA and nucleocapsid domains. Structure prediction of MA-tRNA complexes revealed the binding interface unique to the MA-SeCTCA complex, which was verified experimentally. CLIP experiments demonstrated that this interface is specifically needed for the MA binding to SeCTCA but not to other tRNAs. Notably, disruption of this interface altered Gag localization pattern, reduced infectivity of virions, and impaired virus replication in CD4+ T cells. Collectively, our results indicate that SeCTCA tRNA binds the HIV-1 Gag MA domain with high specificity and promotes virion formation and efficient replication in T cells.

microbiology↗

bioRxiv2026

Z-Hunt-DP: accelerating thermodynamic Z-DNA prediction with dynamic programming

Z-DNA is a left-handed DNA conformation implicated in gene regulation and chromatin dynamics. Because it is usually less thermodynamically favorable than canonical B-DNA under physiological conditions, computational tools are needed to identify sequences likely to adopt the Z conformation. Legacy Z-Hunt uses a dinucleotide thermodynamic model, but searches every anti/syn assignment in a window, causing its conformation search to grow exponentially with window size. We present Z-Hunt-DP, an exact dynamic programming reformulation that preserves the original thermodynamic objective while reducing this search from O(2^d) to O(d) for a window of d dinucleotide positions. On benchmark windows, Z-Hunt-DP matched the brute-force minimum energy within numerical tolerance and achieved a 3.30x10^5 speedup at 20 dinucleotides. In an interval-localization benchmark on public human loci with experimentally mapped Z-DNA, it recovered the clipped reference interval in all 24 cases and was the most stable localizer under midpoint-core and expanded-panel analyses. Since the comparison set mixes thermodynamic, heuristic, and learned models, these cross-tool results are interpreted as localization comparisons rather than direct thermodynamic score tests. The source code and benchmark materials are available at https://github.com/Aljumaily/Z-Hunt-DP.

bioinformatics↗

bioRxiv2025

Exploring chemotaxis in spatio-temporal stoichiometric models of metabolism: Pseudomonas simiae as a case study

Summary/AbstractChemotaxis is the movement of cells or organisms in the direction of an increasing or decreasing gradient of a chemical, i.e. a chemoattractant or chemorepellent, respectively. In bacteria, this movement is typically manifested through the presence of bias in the random walk generated by run-and-tumble motility. Often, the chemoattractant is consumed by the organism, thus coupling the biophysical, directed motion with the biochemical, metabolic activity in the growing bacterial colony. In this chapter, we describe our approach to simulating chemotaxis, coupled with detailed metabolic activity, within the framework of our modeling software COMETS (Computation of Microbial Ecosystem in Time and Space). By combining genome-scale metabolic models, dynamic flux balance analysis and the newly implemented biophysical chemotaxis model, we built and qualitatively tested a chemotaxis module for COMETS. We applied this model to an automatically constructed genome-scale model of the plant commensal bacterium Pseudomonas simiae WCS417, which we hypothesized would perform chemotaxis on amino acids similar to its close relative Pseudomonas putida. COMETS simulations recapitulated the typical ring colony pattern, which is due to propagation at the colony front, indicative of bacteria growing on a chemoattractant-filled plate. By allowing for detailed examination of spatial distributions and time dynamics of the biomass, as well as concentration profiles of the metabolites involved in the growth and chemotaxis in bacterial colonies, the software method described here enables simulations of complex microbial patterns involving metabolism and directed motility. Beyond testing the appearance of the ring, future model validation could include comparisons of local growth rates and metabolic fluxes, including rates of metabolite uptake and secretion. The newly added COMETS chemotaxis capability integrates flux balance modeling with gradient-induced biomass propagation, paving the way for more realistic simulations of microbial ecosystem dynamics in complex environments, such as plant roots, where chemotaxis may play a fundamental role in microbiome-host dynamics.

systems biology↗

bioRxiv2018

A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.

developmental biology↗