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bioRxiv · 10.1101/2025.07.28.667248

A Multi-Layered Transcriptomic Analysis Sheds Light on Antisense Transcription, RNA Processing, and SmAP Interactions in Sulfolobus acidocaldarius

Brück, M.·Daume, M.·Randau, L.·Gomes-Filho, J. V.
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Abstract

The archaeal domain contains organisms that are well-adapted to extreme conditions and changes in their habitat. Post-transcriptional regulation plays a key role in environmental adaptation, including rapid molecular responses to stress conditions. To understand the importance of RNA-based post-transcriptional regulation for these processes, a comprehensive analysis of the presence and processing of regulatory RNAs, as well as their interactions with other RNAs and proteins, is indispensable. Here, we combine the analysis of several RNA sequencing approaches to reveal the presence of a set of novel non-coding RNAs (ncRNAs), their expression in various conditions, processing, and molecular interactions in the transcriptome of Sulfolobus acidocaldarius, a model organism for Archaea. We expand its annotation by 160 intergenic ncRNAs (sRNAs) and 990 antisense RNAs (asRNAs), add the location and motifs of over 6000 transcript processing sites, and determine the interaction of transcripts with Sm-like archaeal proteins (SmAPs). We determined the correlation between the expression patterns of asRNAs and their cognate mRNAs, suggesting transcript-based regulation patterns in gene expression, particularly in response to changing environmental conditions. Additionally, we observed differential binding preferences of SmAP1 and SmAP2 towards mRNA and ncRNAs, suggesting a distribution of regulating roles of these chaperones. Finally, we provide an overview of our post-transcriptional data analysis results, optimized for custom exploration, in the form of a web-based transcriptome atlas (https://vicentebr.github.io/Sulfolobus_atlas/). IMPORTANCEPost-transcriptional regulation is a key control layer in gene expression. Yet, resources integrating asRNAs, RNA processing sites, and RNA-protein interactions are scarce for archaeal organisms. Here we combine multiple RNA-seq strategies and RIP-seq to expand the Sulfolobus acidocaldarius transcriptome with 990 asRNAs, thousands of transcript processing sites, and the interactomes of the essential RNA chaperones SmAP1 and SmAP2. Integrating the novel generated data for the re-analysis of heat-shock transcriptomics and proteomics reveals locus-specific antisense mechanisms that might help to explain the weak correlation between cellular RNA and protein levels reported previously. Moreover, our publicly accessible web atlas provides a community platform to explore these datasets and assist in the formulation of new hypotheses about archaeal RNA regulation.

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Brück, M., Daume, M., Randau, L., Gomes-Filho, J. V.. 2025-08-02. A Multi-Layered Transcriptomic Analysis Sheds Light on Antisense Transcription, RNA Processing, and SmAP Interactions in Sulfolobus acidocaldarius. https://doi.org/10.1101/2025.07.28.667248

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