Biology subjects

Pavan, S.

Publications and source records attributed to Pavan, S..

4 recordsLinked to original sources

bioRxiv2026

Sustained presence of metabolically active mesophiles in the boiling vent-water of a low-salinity, slightly-alkaline, sulfate-rich geothermal spring characterized by an inequitable ecology of hyperthermophiles and thermophiles

Geothermal vent-heads exclusively support the proliferation of (hyper)thermophilic microorganisms. However, diverse mesophiles are stochastically thrust into these ecosystems by local geodynamic forces, and their population-level responses to the unfamiliar stressor hold critical implications for lifes intrinsic resilience to biophysical adversities. Here, we report a time-course exploration of the boiling vent-water of a Trans-Himalayan geothermal spring to determine the population dynamics, in situ functionalities, and potential ecological roles of mesophilic incomers in the context of indigenous (hyper)thermophiles. The temporally-consistent (hyper)thermophilic core-community, predominated in turn by a few Aquificia and Thermoproteota, was delineated as metagenome-assembled genomes. Mesophiles/moderate-thermophiles were identified as MAGs and/or pure-cultures, and whether temporally-consistent/inconsistent, had far lower prevalence. Overall, in situ transcriptional activity and prevalence had significant positive correlation; but many species exhibited high activity despite low prevalence and vice versa, implicating the decoupling of global metabolism from growth/proliferation. Bulked metatranscriptomic signatures identified the (hyper)thermophiles as primary producers of the ecosystem. Populations of mesophiles and moderate-thermophiles were apparently active, but not growing, in situ, with some being engaged in environment detoxification, and production of nutrients, metabolites and protective-biomolecules wanting in the (hyper)thermophiles. The findings engender an unprecedented portrayal of geothermal-vents as multi-community ecosystems where unfamiliar immigrants provide critical metabolic services.

microbiology↗

bioRxiv2025

A bipartite, mutation-tolerant NLS regulates interaction of ΔNp63α with importin alpha, nuclear transport and transcriptional activity

{Delta}Np63 is a master regulator of epithelial development, driving the expansion of progenitor cells in stratified epithelia. Mutations in {Delta}Np63 are linked to squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), as well as to ectodermal dysplasia syndromes such as ectrodactyly-ectodermal dysplasia-clefting (EEC) and ankyloblepharon-ectodermal dysplasia-clefting (AEC). Although {Delta}Np63 functions as a nuclear transcription factor, the mechanisms underlying its nuclear import remain incompletely understood. By combining imaging, biochemical, structural and functional assays, we have thoroughly characterized {Delta}Np63 nuclear import, as mediated by the importin (IMP) /{beta}1 heterodimer. We also show here that {Delta}Np63 has evolved a peculiar strategy to ensure mutation tolerant nuclear localization, which is essential for DNA binding and transcriptional regulation. Despite a canonical bipartite NLS formed by two stretches of basic amino acids was identified between the DNA binding and oligomerization domains, each of them in sufficient to bind both IMP binding sites upon homodimerization. Therefore, in contrast to most known bipartite NLSs, only simultaneous substitution of both basic stretches of amino acids ablated nuclear localization, interaction with IMP, and decreased transcriptional activity. Since several {Delta}Np63 isoforms which lack the N-terminal basic stretch of amino acids have been described, and a number of mutations in the {Delta}Np63 NLS region have been identified in the Genome Aggregation Database, {Delta}Np63 has specifically evolved to tolerate mutations in its NLS without significantly compromising its ability to localize in the nucleus. GRAPHICAL ABSTRACT

cell biology↗

bioRxiv2025

Importin α/β1 dependent nuclear import of Black Sea Bass Polyomavirus Large Tumor Antigen is mediated by a classical NLS located downstream of the SF3 helicase domain

Polyomaviruses (PyVs) are small dsDNA viruses that replicate in the host cell nucleus, primarily relying on the viral encoded large tumor antigen (LTA). Aided by recent advances in molecular biology techniques, the list of known PyVs is rapidly growing, revealing unexpected broad sequence, and host heterogenicity. Given their dependence on nuclear localization, large tumor antigens represent an attractive model for studying the nuclear transport process. A comprehensive analysis of the evolution of classical nuclear localization signals (cNLSs) within LTAs encoded by PyVs infecting mammals highlighted strong positional conservation of cNLSs between the LXCXE motif and the origin-binding domain (OBD). Here we extend such analysis to PyVs infecting non-mammalian hosts. We combined biochemical, structural and functional assays to demonstrate that Black Sea Bass (BSB) PyV-LTA is transported into the nucleus by the Importin (IMP)/{beta}1 heterodimer thanks to the recognition of a bipartite cNLS located downstream of the SF3 helicase domain, rather than between the LXCXE motif and the OBD. Such cNLS binds with high affinity to several IMP isoforms by simultaneously interacting with the minor and major binding sites. Substitution of NLS key basic residues abrogating binding to IMP, or co-expression with the well characterized IMP/{beta}1 inhibitor Bimax2 suppressed nuclear localization. Intriguingly a cNLS could be identified in a similar position in LTAs from other PyVs infecting ray-finned fishes, but not cartilaginous fishes, birds or scorpions, where cNLSs were predicted elsewhere. Our study suggests that LTAs from PyVs infecting different non-mammalian hosts might bear cNLS in distinctive positions, possibly reflecting processes of virus-host adaptation.

microbiology↗

bioRxiv2025

Nuclear trafficking of Anelloviridae capsid protein ORF1 reflects modular evolution of subcellular targeting signals

Anelloviridae members are ubiquitous viruses with a small, negative sense, single-stranded DNA genome which is replicated by host cell DNA polymerases. Anelloviruses are postulated to interact with the host cell nuclear transport machinery, however, the lack of reliable cell culture models strongly limits our knowledge regarding Anelloviridae-host interactions. In particular, capsid nuclear import is a largely uncharacterized process. We addressed this by investigating the relationship between host cell nuclear transport receptors (NTRs) and ORF1, the putative capsid protein from torque teno douroucouli virus (TTDoV). We identified the subcellular targeting signals and NTRs responsible for its nucleolar and nuclear localization, and characterized their relative contribution to ORF1 subcellular localization. In the absence of other viral proteins, ORF1 accumulated in the nucleoli. Bioinformatics analysis revealed a putative nuclear localization signal (NLS) within the highly conserved N-terminal arginine rich motif (ARM) ("NLSn", 27-RRWRRRPRRRRRPYR-RRPYRRYGRRRKVRRR-57), and an additional C-terminal NLS ("NLSc", 632-LPPPEKRARWGF-643), which has been specifically acquired by Anelloviridae capsids with larger projection domains. Such NLSs play distinct roles in ORF1 subcellular localization. NLSn features broad importin (IMP) binding affinity yet plays a minor role in nuclear import, being responsible for nucleolar targeting likely through interaction with nucleolar components. NLSc specifically interacts with IMP and is the main driver of active nuclear transport in an IMP/{beta}1-dependent fashion. These findings suggest an evolutionary correlation between the acquisition of progressively larger projection domains and the presence of additional NLSs in Anelloviridae capsids, aimed at maximizing IMP/{beta}1-mediated nuclear import.

microbiology↗