Riboregulation by DsrA RNA: trans‐actions for global economy

DsrA is an 87 nucleotide Escherichia coli RNA with extraordinary regulatory properties. The profound impact of its actions stems from DsrA regulating translation of two global transcription regulators, H‐NS and RpoS (σs), by sequence‐specific RNA–RNA interactions. H‐NS is a major nucleoid‐structuring and global repressor protein, and RpoS is the stationary phase and stress response sigma factor of RNA polymerase. DsrA changes its conformation to bind to these two different mRNA targets and thereby inhibits H‐NS translation, while stimulating that of RpoS in a mechanistically distinct fashion. DsrA apparently binds both the start and the stop codons of hns mRNA and sharply decreases the mRNA half‐life. DsrA also binds sequences in the 5′‐untranslated leader region of rpoS mRNA, enhancing rpoS mRNA stability and RpoS translation. A cohort of genes, governed by H‐NS repression and RpoS activation, are thus regulated. Low temperatures increase the levels of DsrA, with differential effects on H‐NS and RpoS. Additionally, the RNA chaperone protein Hfq is involved with DsrA regulation, as well as with other small RNAs that also act on RpoS to co‐ordinate stress responses. We address the possible functions of this genetic regulatory mechanism, as well as the advantages of using small RNAs as global regulators to orchestrate gene expression.

[1]  B. Ganem.  RNA world , 1987, Nature.

[2]  M. Inouye,et al.  Small RNAs in the prokaryotes: A growing list of diverse roles , 1988, Cell.

[3]  R. Hengge-aronis,et al.  The role of the sigma factor sigma S (KatF) in bacterial global regulation. , 1994, Annual review of microbiology.

[4]  S. Gottesman,et al.  A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. Herschlag.  RNA Chaperones and the RNA Folding Problem (*) , 1995, The Journal of Biological Chemistry.

[6]  M. Belfort,et al.  Escherichia coli protein StpA stimulates self-splicing by promoting RNA assembly in vitro. , 1995, RNA.

[7]  N. Delihas,et al.  Regulation of gene expression by trans‐encoded antisense RNAs , 1995, Molecular microbiology.

[8]  B. Uhlin,et al.  Coordinated and differential expression of histone‐like proteins in Escherichia coli: regulation and function of the H‐NS analog StpA. , 1996, The EMBO journal.

[9]  R. Hengge-aronis,et al.  Back to log phase: σS as a global regulator in the osmotic control of gene expression in Escherichia coli , 1996, Molecular microbiology.

[10]  M. Belfort,et al.  Escherichia coli protein analogs StpA and H‐NS: regulatory loops, similar and disparate effects on nucleic acid dynamics. , 1996, The EMBO journal.

[11]  S. Gottesman,et al.  The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli. , 1996, The EMBO journal.

[12]  H. Ingmer,et al.  H‐NS: a modulator of environmentally regulated gene expression , 1997, Molecular microbiology.

[13]  R M Williams,et al.  Molecular aspects of the E. coli nucleoid protein, H-NS: a central controller of gene regulatory networks. , 1997, FEMS microbiology letters.

[14]  R. Hengge-aronis,et al.  The RNA-binding protein HF-I plays a global regulatory role which is largely, but not exclusively, due to its role in expression of the sigmaS subunit of RNA polymerase in Escherichia coli , 1997, Journal of bacteriology.

[15]  M. Winkler,et al.  Altered 3'-terminal RNA structure in phage Qbeta adapted to host factor-less Escherichia coli. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Elliott,et al.  Mutations that increase expression of the rpoS gene and decrease its dependence on hfq function in Salmonella typhimurium , 1997, Journal of bacteriology.

[17]  G. Storz,et al.  A Small, Stable RNA Induced by Oxidative Stress: Role as a Pleiotropic Regulator and Antimutator , 1997, Cell.

[18]  Jürgen Böhringer,et al.  The LysR‐like regulator LeuO in Escherichia coli is involved in the translational regulation of rpoS by affecting the expression of the small regulatory DsrA‐RNA , 1997, Molecular microbiology.

[19]  M. Winkler,et al.  Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12 , 1997, Journal of bacteriology.

[20]  M. Cusick,et al.  Domain structure and RNA annealing activity of the Escherichia coli regulatory protein StpA , 1998, Molecular microbiology.

[21]  G. Storz,et al.  The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF‐I) protein , 1998, The EMBO journal.

[22]  M. Cusick,et al.  Riboregulation in Escherichia coli: DsrA RNA acts by RNA:RNA interactions at multiple loci. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G. Storz,et al.  The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding , 1998, The EMBO journal.

[24]  S. P. Sineoky,et al.  RecA-independent pathways of lambdoid prophage induction in Escherichia coli. , 1998, Journal of bacteriology.

[25]  T. Romeo,et al.  Global regulation by the small RNA‐binding protein CsrA and the non‐coding RNA molecule CsrB , 1998, Molecular microbiology.

[26]  S. P. Sineoky,et al.  RecA-Independent Pathways of Lambdoid Prophage Induction in Escherichia coli , 1998 .

[27]  N. Majdalani,et al.  DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Eddy.  Noncoding RNA genes. , 1999, Current opinion in genetics & development.

[29]  R. Schroeder,et al.  Assaying RNA chaperone activity in vivo using a novel RNA folding trap , 1999, The EMBO journal.

[30]  S. Ueda,et al.  Growth Phase-Dependent Variation in Protein Composition of the Escherichia coli Nucleoid , 1999, Journal of bacteriology.

[31]  A. Ishihama,et al.  Twelve Species of the Nucleoid-associated Protein from Escherichia coli , 1999, The Journal of Biological Chemistry.

[32]  G. Storz,et al.  Small RNAs in Escherichia coli. , 1999, Trends in microbiology.

[33]  R. Lease,et al.  A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures. , 2000, Proceedings of the National Academy of Sciences of the United States of America.