Felder, S. | Search bioRxiv

bioRxiv2026

RNA Structure Coordinates Translation Across the Meiotic Program

mRNA structure clearly modulates translation efficiency for individual transcripts, yet its role in coordinating translation across many transcripts remains poorly defined. Meiosis offers a compelling test case, involving large-scale gene expression changes coordinated across hundreds of mRNAs under conditions where transcription is constrained by chromosome condensation. We profiled mRNA structures across yeast meiosis, generating a high-resolution structurome encompassing ~70% of annotated mRNAs, including multi-time-point measurements for 2,084 transcripts. Transcripts upregulated during meiosis generally adopt flexible structures that enhance translation, whereas mRNAs with complex 5' UTR and coding-region structures show suppressed translation, indicating that RNA structure globally shapes meiotic translation. We further observed a high-low-high oscillation in cytoplasmic RNA helicase levels across meiosis. Together, these findings support a model in which RNA structure and helicase expression act jointly to program stage-specific translation of hundreds of mRNAs, with highly structured transcripts selectively translated at late stages. Consistent with this model, disrupting the structure of the abundant transcript CCW22, or altering Ded1p helicase levels, impaired meiotic progression in an RNA structure-dependent manner. Our study reveals that the concerted action of RNA structure and helicases coordinates cell-wide translation dynamics to meet stage-specific demands, especially critical when transcription is limited during meiotic divisions.

genomics↗

bioRxiv2025

fpocketR: A platform for identification and analysis of ligand-binding pockets in RNA

Small molecules that bind specific sites in RNAs hold promise for altering RNA function, manipulating gene expression, and expanding the scope of druggable targets beyond proteins. Identifying binding sites in RNA that can engage ligands with good physicochemical properties remains a significant challenge. fpocketR is a software and framework for identifying, characterizing, and visualizing ligand-binding sites in RNA. fpocketR was optimized, through a comprehensive analysis of currently available RNA-ligand complexes, to identify pockets in RNAs able to bind small molecules possessing favorable properties, generally termed drug-like. Here, we demonstrate multiple, complex, uses of fpocketR to analyze RNA-ligand interactions and novel pockets in small and large RNAs, to assess ensembles of RNA structure models, to identify pockets in dynamic RNA systems, and to evaluate the shapes of RNA pockets. fpocketR performs best with RNA structures visualized at atomistic resolution but also provides useful information with lower resolution structures and computational models. fpocketR is a powerful, ligand-agnostic tool for discovery and analysis of targetable pockets in RNA molecules.

bioinformatics↗