TY - JOUR
T1 - REP sequences
T2 - Mediators of the environmental stress response?
AU - Liang, Wenxing
AU - Deutscher, Murray P.
N1 - Funding Information:
This work was supported by Grant GM16317 from the National Institutes of Health to M.P.D., and grants 31370779 from the National Natural Science Foundation of China and from the Taishan Scholar Construction Foundation of Shandong Province to W.L.
Publisher Copyright:
© 2016 Taylor & Francis Group, LLC.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - ABSTRACT: Repetitive Extragenic Palindromic (REP) sequences are highly conserved, structured, 35- to 40-nt elements located at ∼500 positions around the Escherichia coli chromosome. They are found in intergenic regions and are transcribed together with their upstream genes. Although their stable stem-loop structures protect messages against exoribonuclease digestion, their primary function has remained unknown. Recently, we found that about half of all REP sequences have the potential to stall ribosomes immediately upstream of the termination codon, leading to endonucleolytic cleavage of the mRNA, and induction of the trans-translation process. As a consequence, the mRNA and almost completed protein are degraded, and protein production from the affected gene is down-regulated. The process is critically dependent on the location of the REP element, with an effect only if it is within 15 nt of the termination codon. Using nrdAB as a model, we found that its down-regulation is affected by RNA helicases. Elimination of 6 helicases lowered NrdA production further, whereas overexpression of any RNA helicase partially reversed the downregulation. UV stress completely reversed down-regulation of NrdA production. Analysis of genes containing a REP sequence within 15 nt of the termination codon revealed that most, if not all, are up-regulated by environmental stress, as are RNA helicases. Based on these findings, we propose that REP-dependent downregulation serves as a mechanism to allow a rapid response to environmental stresses whereby RNA helicases partially open the REP elements enabling ribosomes to complete translation immediately increasing protein production from the affected genes.
AB - ABSTRACT: Repetitive Extragenic Palindromic (REP) sequences are highly conserved, structured, 35- to 40-nt elements located at ∼500 positions around the Escherichia coli chromosome. They are found in intergenic regions and are transcribed together with their upstream genes. Although their stable stem-loop structures protect messages against exoribonuclease digestion, their primary function has remained unknown. Recently, we found that about half of all REP sequences have the potential to stall ribosomes immediately upstream of the termination codon, leading to endonucleolytic cleavage of the mRNA, and induction of the trans-translation process. As a consequence, the mRNA and almost completed protein are degraded, and protein production from the affected gene is down-regulated. The process is critically dependent on the location of the REP element, with an effect only if it is within 15 nt of the termination codon. Using nrdAB as a model, we found that its down-regulation is affected by RNA helicases. Elimination of 6 helicases lowered NrdA production further, whereas overexpression of any RNA helicase partially reversed the downregulation. UV stress completely reversed down-regulation of NrdA production. Analysis of genes containing a REP sequence within 15 nt of the termination codon revealed that most, if not all, are up-regulated by environmental stress, as are RNA helicases. Based on these findings, we propose that REP-dependent downregulation serves as a mechanism to allow a rapid response to environmental stresses whereby RNA helicases partially open the REP elements enabling ribosomes to complete translation immediately increasing protein production from the affected genes.
KW - RNA helicase
KW - mRNA
KW - ribosome
KW - stress response
KW - trans-translation
KW - translational regulation
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U2 - 10.1080/15476286.2015.1112489
DO - 10.1080/15476286.2015.1112489
M3 - Article
C2 - 26574793
AN - SCOPUS:84961238068
VL - 13
SP - 152
EP - 156
JO - RNA Biology
JF - RNA Biology
SN - 1547-6286
IS - 2
ER -