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bioRxiv · 10.64898/2026.08.26.747414

Temperature-driven isoform switching reprograms developmental gene expression in a human fungal pathogen

Kalem, M. C.·Voorhies, M.·Markman, N.·Sil, A.
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Abstract

Post-transcriptional regulation is key to development, and yet little is known about how RNA isoform choice contributes to developmental choices in fungi. Here we assemble the first isoform-level transcriptome of Histoplasma, a ubiquitous human fungal pathogen that grows as an infectious environmental form (hyphae) or a pathogenic host form (yeast) in response to temperature. We find extensive morphology-associated longer leader and trailer isoforms, rapid temperature-driven transcription start site remodeling, and inclusion of regulatory elements in longer leaders. We observe isoform-specific patterns of ribosome and polysome association, indicating that isoform switching regulates the proteome. Our results suggest a model in which isoform diversity and rapid isoform switching are central to post-transcriptional regulation during thermal dimorphism, enabling precise and timely translation of factors needed to establish and maintain hyphal and yeast forms. These studies illuminate how eukaryotic systems utilize post- transcriptional regulation to determine developmental states in response to external stimuli.

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Kalem, M. C., Voorhies, M., Markman, N., Sil, A.. 2026-08-27. Temperature-driven isoform switching reprograms developmental gene expression in a human fungal pathogen. https://doi.org/10.64898/2026.08.26.747414

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