6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase

Bacterial RNA polymerases (RNAP) utilize 6S RNAs as templates to synthesize ultrashort transcripts (up to ~14 nt), termed product RNAs (pRNAs), that play a key role in reversing the blockage of RNAP by 6S RNA. Here, we resolved the pRNA length profile of 6S-1 RNA from B. subtilis, a major model syst...

Full description

Saved in:
Bibliographic Details
Main Authors: Katrin Damm, Paul Klemm, Marcus Lechner, Dominik Helmecke, Roland K. Hartmann
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:RNA Biology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/15476286.2025.2484519
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849726546498027520
author Katrin Damm
Paul Klemm
Marcus Lechner
Dominik Helmecke
Roland K. Hartmann
author_facet Katrin Damm
Paul Klemm
Marcus Lechner
Dominik Helmecke
Roland K. Hartmann
author_sort Katrin Damm
collection DOAJ
description Bacterial RNA polymerases (RNAP) utilize 6S RNAs as templates to synthesize ultrashort transcripts (up to ~14 nt), termed product RNAs (pRNAs), that play a key role in reversing the blockage of RNAP by 6S RNA. Here, we resolved the pRNA length profile of 6S-1 RNA from B. subtilis, a major model system for the study of 6S RNA biology, during outgrowth of cells from extended stationary phase. 9-mers were found to be a particularly abundant pRNA length species, followed by 8-/10-/11-mers and 13-/14-mers. Consistent with in vitro data from the Escherichia coli system, these findings support the mechanistic model according to which the housekeeping sigma factor (σ70 or σA) dissociates from 6S RNA:RNAP complexes upon synthesis of pRNA 9-mers, followed by final dissociation of 6S RNA and RNAP upon synthesis of longer pRNAs (13-/14-mers). Methodologically, the identification of such ultrashort RNAs in total cellular extracts by RNA-Seq is inefficient with standard protocols using adapter ligation to RNA 3’-ends for reverse transcription and PCR-based cDNA sequencing. Here, we demonstrate that ultrashort RNAs can instead be incorporated into RNA-Seq libraries by polyA-, polyC- and potentially also polyU-tailing of their 3’-ends. At positions where a non-tailing nucleotide is followed by one or more tailing nucleotides, an algorithm that integrates RNA-Seq results from at least two different 3’-end tailings allows one to approximate the fraction of read counts at such ambiguous positions. Finally, methodological biases and potential applications of our approach to other short RNAs are discussed.
format Article
id doaj-art-658d7747f3b9476e95b52eed55bbe0ca
institution DOAJ
issn 1547-6286
1555-8584
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series RNA Biology
spelling doaj-art-658d7747f3b9476e95b52eed55bbe0ca2025-08-20T03:10:09ZengTaylor & Francis GroupRNA Biology1547-62861555-85842025-12-0122111410.1080/15476286.2025.24845196S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phaseKatrin Damm0Paul Klemm1Marcus Lechner2Dominik Helmecke3Roland K. Hartmann4Fachbereich Pharmazie, Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, GermanyCenter for Synthetic Microbiology (SYNMIKRO), Philipps-Universität Marburg, Marburg, GermanyCenter for Synthetic Microbiology (SYNMIKRO), Philipps-Universität Marburg, Marburg, GermanyFachbereich Pharmazie, Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, GermanyFachbereich Pharmazie, Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, GermanyBacterial RNA polymerases (RNAP) utilize 6S RNAs as templates to synthesize ultrashort transcripts (up to ~14 nt), termed product RNAs (pRNAs), that play a key role in reversing the blockage of RNAP by 6S RNA. Here, we resolved the pRNA length profile of 6S-1 RNA from B. subtilis, a major model system for the study of 6S RNA biology, during outgrowth of cells from extended stationary phase. 9-mers were found to be a particularly abundant pRNA length species, followed by 8-/10-/11-mers and 13-/14-mers. Consistent with in vitro data from the Escherichia coli system, these findings support the mechanistic model according to which the housekeeping sigma factor (σ70 or σA) dissociates from 6S RNA:RNAP complexes upon synthesis of pRNA 9-mers, followed by final dissociation of 6S RNA and RNAP upon synthesis of longer pRNAs (13-/14-mers). Methodologically, the identification of such ultrashort RNAs in total cellular extracts by RNA-Seq is inefficient with standard protocols using adapter ligation to RNA 3’-ends for reverse transcription and PCR-based cDNA sequencing. Here, we demonstrate that ultrashort RNAs can instead be incorporated into RNA-Seq libraries by polyA-, polyC- and potentially also polyU-tailing of their 3’-ends. At positions where a non-tailing nucleotide is followed by one or more tailing nucleotides, an algorithm that integrates RNA-Seq results from at least two different 3’-end tailings allows one to approximate the fraction of read counts at such ambiguous positions. Finally, methodological biases and potential applications of our approach to other short RNAs are discussed.https://www.tandfonline.com/doi/10.1080/15476286.2025.2484519RNA-SeqIllumina sequencingpolyA/C/U-tailingpolyA/U polymerasepRNAsBacillus subtilis 6S-1 RNA
spellingShingle Katrin Damm
Paul Klemm
Marcus Lechner
Dominik Helmecke
Roland K. Hartmann
6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
RNA Biology
RNA-Seq
Illumina sequencing
polyA/C/U-tailing
polyA/U polymerase
pRNAs
Bacillus subtilis 6S-1 RNA
title 6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
title_full 6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
title_fullStr 6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
title_full_unstemmed 6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
title_short 6S-1 pRNA 9-mers are a prominent length species during outgrowth of Bacillus subtilis cells from extended stationary phase
title_sort 6s 1 prna 9 mers are a prominent length species during outgrowth of bacillus subtilis cells from extended stationary phase
topic RNA-Seq
Illumina sequencing
polyA/C/U-tailing
polyA/U polymerase
pRNAs
Bacillus subtilis 6S-1 RNA
url https://www.tandfonline.com/doi/10.1080/15476286.2025.2484519
work_keys_str_mv AT katrindamm 6s1prna9mersareaprominentlengthspeciesduringoutgrowthofbacillussubtiliscellsfromextendedstationaryphase
AT paulklemm 6s1prna9mersareaprominentlengthspeciesduringoutgrowthofbacillussubtiliscellsfromextendedstationaryphase
AT marcuslechner 6s1prna9mersareaprominentlengthspeciesduringoutgrowthofbacillussubtiliscellsfromextendedstationaryphase
AT dominikhelmecke 6s1prna9mersareaprominentlengthspeciesduringoutgrowthofbacillussubtiliscellsfromextendedstationaryphase
AT rolandkhartmann 6s1prna9mersareaprominentlengthspeciesduringoutgrowthofbacillussubtiliscellsfromextendedstationaryphase