Biology subjects

Tripathi, I.

Publications and source records attributed to Tripathi, I..

3 recordsLinked to original sources

bioRxiv2026

The fidelity of mRNA translation as a novel regulatory layer for brain development

Although the fidelity of mRNA translation is essential for maintaining proteome integrity, whether translation error rates vary across cell types and developmental stages in vivo remains largely unexplored. Here, we generate a gain-of-activity dual-luciferase knock-in reporter mouse that enables quantitative monitoring of translation errors in vivo. Using this system, we systematically characterize the spatiotemporal dynamics of translation fidelity across mammalian development. Mature organs exhibit lower error rates than pluripotent embryonic stem cells. Translation fidelity diverges sharply among organs, becoming progressively established during embryonic development, with brain and muscle displaying the highest accuracy. To determine functional significance, we experimentally increased translation errors during cerebral organoid formation and in vitro neuronal differentiation. Elevated error rates reduced neuronal output by impairing neuronal maturation without altering neural progenitor populations. Consistently, differentiated neurons display uniformly elevated fidelity across multiple classes of translation errors, including stop codon readthrough, amino acid misincorporation, and ribosomal frameshifting. These findings demonstrate that translation fidelity is not a fixed intrinsic property of the translation machinery but is developmentally regulated and required for efficient neuronal differentiation. Together, our results identify translation fidelity as a developmentally tuned, tissue-specific dimension of gene expression in vivo.

developmental biology↗

bioRxiv2025

Central carbon metabolism switching in lytic versus temperate coral reef viral communities

Coral reefs are declining globally due in part to bacterial overgrowth, a process known as microbialization. However, the role of bacteriophages that may inhibit microbialization by infecting and killing these bacteria remains poorly understood, especially their metabolic impacts on bacterial proliferation. To address this, we analyzed central carbon metabolism gene frequencies in viral communities from healthy (lytic-dominated) and degraded (temperate-dominated) Central Pacific coral reefs. We found that viral metabolism shifted broadly from being dominated by metabolism that builds up pools of central intermediates on degraded reefs dominated by temperate viral infection ("anaplerotic" reactions) to metabolism that consumes these pools to prioritize production of metabolic precursors for virion construction on healthy reefs dominated by lytic infection ("cataplerotic" reactions). This switch was shown by the over-representation of Entner-Doudoroff (ED) glycolysis genes on degraded, temperate-dominated reefs and of pentose phosphate pathway (PPP) and reductive tricarboxylic acid cycle (TCA) genes on healthy, lytic-dominated reefs. As a result of this metabolic dichotomy, our qualitative compartment modeling revealed two distinct ecosystem states: (i) healthy reefs, where lytic viral metabolism enhances viral production and suppresses bacterial overgrowth, and (ii) degraded reefs, where temperate viral metabolism accelerates bacterial proliferation. Because viral switching between lytic and temperate lifestyles is a known function of host physiological state, these findings position viral metabolism as both a driver of reef decline and a conservation lever, with metabolically mediated "re-viralization" offering a novel strategy to restore reef resilience.

ecology↗

bioRxiv2025

Transitions in human gut viral communities from ancient to industrialized societies

The composition and function of the human gut microbial community (the microbiome) have changed substantially over millennia, with implications for human health. While microbiome research has focused primarily on bacterial dynamics, the long-term history of gut viral communities (the virome) remains largely unexplored, despite their crucial role in shaping bacterial populations. We analyzed gut viromes from 14 pre-modern human coprolites (1301 BCE-1400s CE), as well as 502 non-industrialized and 492 industrialized contemporary human fecal samples. We found that, from pre-modern to contemporary and industrialized populations, human gut viral communities have become more similar in gene content, increasingly dominated by temperate lifestyles, and more supportive of bacterial pathogenicity. These synergistic ecological shifts suggest that long-term changes, especially with industrialization, have fundamentally altered the gut virome, likely affecting human health. These insights into historical shifts in gut viral community and function open potential avenues for ecologically grounded therapeutics to enhance gut microbiome resilience.

microbiology↗