Woodward, L. | bioRxiv Science

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↗

bioRxiv2024

circPCMTD1: A protein-coding circular RNA that regulates DNA damage response in BCR/ABL-positive leukemias

Circular RNAs are a novel class of RNA transcripts, which regulate important cellular functions in health and disease. Herein, we report on the functional relevance of the circPCMTD1 transcript in acute leukemias. In screening experiments, we found that circPCMTD1 depletion strongly inhibited the proliferative capacity of leukemic cells with BCR-ABL translocations. Mass cytometry experiments identified the aberrant activation of the DNA damage response as an early downstream event of circPCMTD1 depletion. In in vivo experiments, circPCMTD1 targeting prolonged the survival of mice engrafted with leukemic blasts harboring the Philadelphia chromosome. Mechanistically, we found that circPCMTD1 was enriched in the cytoplasm and associated with the ribosomes of the leukemic cells. We detected a cryptic open reading frame within the circPCMTD1 sequence and found that circPCMTD1 could generate a peptide product. The circPCMTD1-derived peptide interacted with proteins of the BTR complex and enhanced BTR complex formation, thereby increasing tolerance to genotoxic stress.

cancer biology↗