Bacteria employ small non-coding RNAs (sRNAs) to regulate gene expression. Ms1 is an sRNA that binds to the RNA polymerase (RNAP) core and affects the intracellular level of this essential enzyme. Ms1 is structurally related to 6S RNA that binds to a different form of RNAP, the holoenzyme bearing the primary sigma factor. 6S RNAs are widespread in the bacterial kingdom except for the industrially and medicinally important Actinobacteria. While Ms1 RNA was identified in Mycobacterium, it is not clear whether Ms1 RNA is present also in other Actinobacteria species. Here, using a computational search based on secondary structure similarities combined with a linguistic gene synteny approach, we identified Ms1 RNA in Streptomyces. In S. coelicolor, Ms1 RNA overlaps with the previously annotated scr3559 sRNA with an unknown function. We experimentally confirmed that Ms1 RNA/scr3559 associates with the RNAP core without the primary sigma factor HrdB in vivo. Subsequently, we applied the computational approach to other Actinobacteria and identified Ms1 RNA candidates in 824 Actinobacteria species, revealing Ms1 RNA as a widespread class of RNAP binding sRNAs, and demonstrating the ability of our multifactorial computational approach to identify weakly conserved sRNAs in evolutionarily distant genomes.

Laboratory of Bioinformatics Institute of Microbiology of the Czech Academy of Sciences Prague Czechia

Laboratory of Microbial Genetics and Gene Expression Institute of Microbiology of the Czech Academy of Sciences Prague Czechia

Laboratory of Structural Biology and Cell Signaling Institute of Microbiology of the Czech Academy of Sciences Vestec Czechia

Zobrazit více v PubMed

Allen T. A., Von Kaenel S., Goodrich J. A., Kugel J. F. (2004). The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. PubMed DOI

Arnvig K. B., Comas I., Thomson N. R., Houghton J., Boshoff H. I., Croucher N. J., et al. (2011). Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of PubMed DOI PMC

Barquist L., Burge S. W., Gardner P. P. (2016). Studying RNA homology and conservation with infernal: from single sequences to RNA families. PubMed DOI PMC

Barrick J. E., Sudarsan N., Weinberg Z., Ruzzo W. L., Breaker R. R. (2005). 6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter. PubMed DOI PMC

Beckmann B. M., Burenina O. Y., Hoch P. G., Kubareva E. A., Sharma C. M., Hartmann R. K. (2011). In vivo and in vitro analysis of 6S RNA-templated short transcripts in PubMed DOI

Beckmann B. M., Hoch P. G., Marz M., Willkomm D. K., Salas M., Hartmann R. K. (2012). A pRNA-induced structural rearrangement triggers 6S-1 RNA release from RNA polymerase in PubMed DOI PMC

Behra P. R. K., Pettersson B. M. F., Das S., Dasgupta S., Kirsebom L. A. (2019). Comparative genomics of PubMed DOI PMC

Bellier A., Gominet M., Mazodier P. (2006). Post-translational control of the PubMed DOI

Benson D. R., Brooks J. M., Huang Y., Bickhart D. M., Mastronunzio J. E. (2011). The biology of Frankia sp. strains in the post-genome era. PubMed DOI

Bentley S. D., Chater K. F., Cerdeno-Tarraga A. M., Challis G. L., Thomson N. R., James K. D., et al. (2002). Complete genome sequence of the model actinomycete PubMed DOI

Bobek J., Mikulová A., Šetinová D., Elliot M., Çihák M. (2021). 6S-Like scr3559 RNA affects development and antibiotic production in PubMed DOI PMC

Brown K. L., Wood S., Buttner M. J. (1992). Isolation and characterization of the major vegetative RNA polymerase of PubMed DOI

Burenina O. Y., Elkina D. A., Migur A. Y., Oretskaya T. S., Evguenieva-Hackenberg E., Hartmann R. K., et al. (2020). Similarities and differences between 6S RNAs from PubMed DOI

Burenina O. Y., Hoch P. G., Damm K., Salas M., Zatsepin T. S., Lechner M., et al. (2014). Mechanistic comparison of PubMed DOI PMC

Cavanagh A. T., Klocko A. D., Liu X., Wassarman K. M. (2008). Promoter specificity for 6S RNA regulation of transcription is determined by core promoter sequences and competition for region 4.2 of sigma70. PubMed DOI

Cavanagh A. T., Sperger J. M., Wassarman K. M. (2012). Regulation of 6S RNA by pRNA synthesis is required for efficient recovery from stationary phase in E. coli and B. subtilis. PubMed DOI PMC

Cavanagh A. T., Wassarman K. M. (2013). 6S-1 RNA function leads to a delay in sporulation in PubMed DOI PMC

Chen J., Wassarman K. M., Feng S., Leon K., Feklistov A., Winkelman J. T., et al. (2017). 6S RNA mimics B-form DNA to regulate PubMed DOI PMC

Elkina D., Weber L., Lechner M., Burenina O., Weisert A., Kubareva E., et al. (2017). 6S RNA in PubMed DOI PMC

Espinoza C. A., Allen T. A., Hieb A. R., Kugel J. F., Goodrich J. A. (2004). B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. PubMed DOI

Faucher S. P., Friedlander G., Livny J., Margalit H., Shuman H. A. (2010). PubMed DOI PMC

Fraser C. M., Gocayne J. D., White O., Adams M. D., Clayton R. A., Fleischmann R. D., et al. (1995). The minimal gene complement of PubMed DOI

Fuchs T., Wiget P., Osterås M., Jenal U. (2001). Precise amounts of a novel member of a phosphotransferase superfamily are essential for growth and normal morphology in PubMed DOI

Gomez M., Doukhan L., Nair G., Smith I. (1998). sigA is an essential gene in PubMed DOI

Han X. X., Luo X. X., Zhang L. L. (2014). PubMed DOI

Hezbri K., Ghodhbane-Gtari F., Montero-Calasanz M. D. C., Nouioui I., Rohde M., Spröer C., et al. (2016). PubMed DOI

Hindley J. (1967). Fractionation of 32P-labelled ribonucleic acids on polyacrylamide gels and their characterization by fingerprinting. PubMed DOI

Hnilicova J., Matejckova J. J., Sikova M., Pospisil J., Halada P., Panek J., et al. (2014). Ms1, a novel sRNA interacting with the RNA polymerase core in mycobacteria. PubMed DOI PMC

Hoch P. G., Burenina O. Y., Weber M. H., Elkina D. A., Nesterchuk M. V., Sergiev P. V., et al. (2015). Phenotypic characterization and complementation analysis of PubMed DOI

Hoch P. G., Schlereth J., Lechner M., Hartmann R. K. (2016). PubMed DOI PMC

Hopwood D. A. (2006). Soil to genomics: the PubMed DOI

Jeong Y., Kim J. N., Kim M. W., Bucca G., Cho S., Yoon Y. J., et al. (2016). The dynamic transcriptional and translational landscape of the model antibiotic producer PubMed DOI PMC

Jones A. J., Venkataramanan K. P., Papoutsakis T. (2016). Overexpression of two stress-responsive, small, non-coding RNAs, 6S and tmRNA, imparts butanol tolerance in PubMed DOI

Kalvari I., Argasinska J., Quinones-Olvera N., Nawrocki E. P., Rivas E., Eddy S. R., et al. (2017). Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families. PubMed DOI PMC

Kim W., Hwang S., Lee N., Lee Y., Cho S., Palsson B., et al. (2020). Transcriptome and translatome profiles of PubMed DOI PMC

Klocko A. D., Wassarman K. M. (2009). 6S RNA binding to Esigma(70) requires a positively charged surface of sigma(70) region 4.2. PubMed DOI PMC

Köhler K., Duchardt-Ferner E., Lechner M., Damm K., Hoch P. G., Salas M., et al. (2015). Structural and mechanistic characterization of 6S RNA from the hyperthermophilic bacterium PubMed DOI

Korf I., Yandell M., Bedell J. (2003).

Labeda D. P., Kroppenstedt R. M. (2004). Emended description of the genus PubMed DOI

Lee Y., Lee N., Hwang S., Kim W., Jeong Y., Cho S., et al. (2020). Genome-scale determination of 5′ and 3′ boundaries of RNA transcripts in PubMed DOI PMC

Lorenz R., Bernhart S. H., Honer Zu Siederdissen C., Tafer H., Flamm C., Stadler P. F., et al. (2011). ViennaRNA Package 2.0. PubMed DOI PMC

Markham N. R., Zuker M. (2008). UNAFold: software for nucleic acid folding and hybridization. PubMed DOI

Martini M. C., Zhou Y., Sun H., Shell S. S. (2019). Defining the transcriptional and post-transcriptional landscapes of. PubMed DOI PMC

Mikulík K., Bobek J., Zídková J., Felsberg J. (2014). 6S RNA modulates growth and antibiotic production in PubMed DOI

Moody M. J., Young R. A., Jones S. E., Elliot M. A. (2013). Comparative analysis of non-coding RNAs in the antibiotic-producing PubMed DOI PMC

Neusser T., Polen T., Geissen R., Wagner R. (2010). Depletion of the non-coding regulatory 6S RNA in PubMed DOI PMC

Nikitina E., Liu S. W., Li F. N., Buyantueva L., Abidueva E., Sun C. H. (2020). sp. nov., an actinobacterium isolated from steppe soil. PubMed DOI

Nouioui I., Carro L., García-López M., Meier-Kolthoff J. P., Woyke T., Kyrpides N. C., et al. (2018). Genome-based taxonomic classification of the phylum. PubMed DOI PMC

Panchapakesan S. S., Unrau P. J. (2012). E. coli 6S RNA release from RNA polymerase requires σ70 ejection by scrunching and is orchestrated by a conserved RNA hairpin. PubMed DOI PMC

Panek J., Bobek J., Mikulik K., Basler M., Vohradsky J. (2008). Biocomputational prediction of small non-coding RNAs in PubMed DOI PMC

Pánek J., Krásny L., Bobek J., Jezková E., Korelusová J., Vohradsky J. (2011). The suboptimal structures find the optimal RNAs: homology search for bacterial non-coding RNAs using suboptimal RNA structures. PubMed DOI PMC

Perez J. T., Varble A., Sachidanandam R., Zlatev I., Manoharan M., García-Sastre A., et al. (2010). tenOever: Influenza a virus-generated small RNAs regulate the switch from transcription to replication. PubMed DOI PMC

Perez J. T., Zlatev I., Aggarwal S., Subramanian S., Sachidanandam R., Kim B., et al. (2012). tenOever: A small-RNA enhancer of viral polymerase activity. PubMed DOI PMC

Rediger A., Geissen R., Steuten B., Heilmann B., Wagner R., Axmann I. M. (2012). 6S RNA - an old issue became blue-green. PubMed DOI

Romero D. A., Hasan A. H., Lin Y. F., Kime L., Ruiz-Larrabeiti O., Urem M., et al. (2014). A comparison of key aspects of gene regulation in PubMed DOI PMC

Schoch C. L., Ciufo S., Domrachev M., Hotton C. L., Kannan S., Khovanskaya R., et al. (2020). NCBI Taxonomy: a comprehensive update on curation, resources and tools. PubMed DOI PMC

Sedlyarova N., Rescheneder P., Magán A., Popitsch N., Rziha N., Bilusic I., et al. (2017). Natural RNA polymerase aptamers regulate transcription in PubMed DOI PMC

Sharma C. M., Hoffmann S., Darfeuille F., Reignier J., Findeiss S., Sittka A., et al. (2010). The primary transcriptome of the major human pathogen PubMed DOI

Shephard L., Dobson N., Unrau P. J. (2010). Binding and release of the 6S transcriptional control RNA. PubMed DOI PMC

Sikova M., Janouskova M., Ramaniuk O., Palenikova P., Pospisil J., Bartl P., et al. (2019). Ms1 RNA increases the amount of RNA polymerase in PubMed DOI

Šmídová K., Ziková A., Pospíšil J., Schwarz M., Bobek J., Vohradsky J. (2019). DNA mapping and kinetic modeling of the HrdB regulon in PubMed DOI PMC

Sridhar J., Gunasekaran P. (2013). Computational small RNA prediction in bacteria. PubMed DOI PMC

Sridhar J., Rafi Z. A. (2007). Small RNA identification in PubMed DOI

Steuten B., Setny P., Zacharias M., Wagner R. (2013). Mapping the spatial neighborhood of the regulatory 6S RNA bound to PubMed DOI

Strnad H., Patek M., Fousek J., Szokol J., Ulbrich P., Nesvera J., et al. (2014). Genome sequence of PubMed DOI PMC

Svensson S. L., Sharma C. M. (2016). Small RNAs in bacterial virulence and communication. PubMed DOI

Trotochaud A. E., Wassarman K. M. (2004). 6S RNA function enhances long-term cell survival. PubMed DOI PMC

Trotochaud A. E., Wassarman K. M. (2005). A highly conserved 6S RNA structure is required for regulation of transcription. PubMed DOI

Trotochaud A. E., Wassarman K. M. (2006). 6S RNA regulation of pspF transcription leads to altered cell survival at high pH. PubMed DOI PMC

Vockenhuber M. P., Sharma C. M., Statt M. G., Schmidt D., Xu Z., Dietrich S., et al. (2011). Deep sequencing-based identification of small non-coding RNAs in PubMed DOI PMC

Vogel D. W., Hartmann R. K., Struck J. C., Ulbrich N., Erdmann V. A. (1987). The sequence of the 6S RNA gene of PubMed DOI PMC

Wassarman K. M. (2018). 6S RNA, a global regulator of transcription. PubMed DOI PMC

Wassarman K. M., Saecker R. M. (2006). Synthesis-mediated release of a small RNA inhibitor of RNA polymerase. PubMed DOI

Wassarman K. M., Storz G. (2000). 6S RNA regulates PubMed DOI

Wehner S., Damm K., Hartmann R. K., Marz M. (2014). Dissemination of 6S RNA among bacteria. PubMed DOI PMC

Wurm R., Neusser T., Wagner R. (2010). 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products. PubMed DOI

Xing K., Qin S., Zhang W. D., Cao C. L., Ruan J. S., Huang Y., et al. (2014). PubMed DOI

Expanding the CarD interaction network: CrsL is a novel transcription regulator in actinobacteria

MoaB2, a newly identified transcription factor, binds to σA in Mycobacterium smegmatis

RIP-seq reveals RNAs that interact with RNA polymerase and primary sigma factors in bacteria

What the Hel: recent advances in understanding rifampicin resistance in bacteria