TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection

Structured RNAs have emerged as a major component of cellular regulatory systems, but their mechanism of action is often poorly understood. Riboswitches are structured RNAs that allosterically regulate gene expression through any of several different mechanisms. In vitro approaches to characterizing...

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Main Authors: Sachit Kshatriya, Sarah C. Bagby
Format: Article
Language:English
Published: PeerJ Inc. 2025-05-01
Series:PeerJ
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Online Access:https://peerj.com/articles/19418.pdf
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author Sachit Kshatriya
Sarah C. Bagby
author_facet Sachit Kshatriya
Sarah C. Bagby
author_sort Sachit Kshatriya
collection DOAJ
description Structured RNAs have emerged as a major component of cellular regulatory systems, but their mechanism of action is often poorly understood. Riboswitches are structured RNAs that allosterically regulate gene expression through any of several different mechanisms. In vitro approaches to characterizing this mechanism are costly, low-throughput, and must be repeated for each individual riboswitch locus of interest. Bioinformatic methods promise higher throughput; despite robust computational identification of riboswitches, however, computational classification of the riboswitch mechanism has so far been both model-bound, relying on identification of sequence motifs known to be required for specific models of riboswitch activity, and empirically untested, with predictions far outpacing biological validation. Here, we introduce TaRTLEt (Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection), a new high-throughput tool that recovers in vivo patterns of riboswitch-mediated transcription termination from paired-end RNA-seq data using edge detection methods. TaRTLEt successfully extracts transcription termination signals despite numerous sources of biological and technical noise. We tested the effectiveness of TaRTLEt on riboswitches identified from a wide range of sequenced bacterial taxa by utilizing publicly available paired-end RNA-seq readsets, finding broad agreement with previously published in vitro characterization results. In addition, we use TaRTLEt to infer the in vivo regulatory mechanism of uncharacterized riboswitch loci from existing public data. TaRTLEt is available on GitHub and can be applied to paired-end RNA-seq datasets from isolates or complex communities.
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spelling doaj-art-37d573d2726e45b9b1f625c5408fe1362025-08-20T03:05:29ZengPeerJ Inc.PeerJ2167-83592025-05-0113e1941810.7717/peerj.19418TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTectionSachit Kshatriya0Sarah C. Bagby1Department of Biology, Case Western Reserve University, Cleveland, OH, United States of AmericaDepartment of Biology, Case Western Reserve University, Cleveland, OH, United States of AmericaStructured RNAs have emerged as a major component of cellular regulatory systems, but their mechanism of action is often poorly understood. Riboswitches are structured RNAs that allosterically regulate gene expression through any of several different mechanisms. In vitro approaches to characterizing this mechanism are costly, low-throughput, and must be repeated for each individual riboswitch locus of interest. Bioinformatic methods promise higher throughput; despite robust computational identification of riboswitches, however, computational classification of the riboswitch mechanism has so far been both model-bound, relying on identification of sequence motifs known to be required for specific models of riboswitch activity, and empirically untested, with predictions far outpacing biological validation. Here, we introduce TaRTLEt (Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection), a new high-throughput tool that recovers in vivo patterns of riboswitch-mediated transcription termination from paired-end RNA-seq data using edge detection methods. TaRTLEt successfully extracts transcription termination signals despite numerous sources of biological and technical noise. We tested the effectiveness of TaRTLEt on riboswitches identified from a wide range of sequenced bacterial taxa by utilizing publicly available paired-end RNA-seq readsets, finding broad agreement with previously published in vitro characterization results. In addition, we use TaRTLEt to infer the in vivo regulatory mechanism of uncharacterized riboswitch loci from existing public data. TaRTLEt is available on GitHub and can be applied to paired-end RNA-seq datasets from isolates or complex communities.https://peerj.com/articles/19418.pdfRiboswitchTranscriptomicsEdge-detectionMechanism
spellingShingle Sachit Kshatriya
Sarah C. Bagby
TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
PeerJ
Riboswitch
Transcriptomics
Edge-detection
Mechanism
title TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
title_full TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
title_fullStr TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
title_full_unstemmed TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
title_short TaRTLEt: Transcriptionally-active Riboswitch Tracer Leveraging Edge deTection
title_sort tartlet transcriptionally active riboswitch tracer leveraging edge detection
topic Riboswitch
Transcriptomics
Edge-detection
Mechanism
url https://peerj.com/articles/19418.pdf
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