title: RNase E autoregulates its synthesis by controlling the degradation rate of its own mRNA in Escherichia coli: unusual sensitivity of the rne transcript to RNase E activity.
abstract: RNase E is a key regulatory enzyme that appears to control the principal pathway for mRNA degradation in Escherichia coli. Here, we show that RNase E represses its own synthesis by reducing the cellular concentration of the rne (RNase E) gene transcript. Autoregulation is achieved by modulating the longevity of this 3.6-kb mRNA, whose half-life ranges from < 40 sec to > 8 min depending on the level of RNase E activity in the cell. Feedback regulation is mediated in cis by the 5'-terminal 0.44-kb segment of rne mRNA, which is sufficient to confer this property onto a heterologous transcript to which it is fused. Like the intact protein, an amino-terminal fragment of RNase E lacking 563 amino acid residues can act in trans to repress rne gene expression. Paradoxically, raising the rne gene copy number 21-fold in E. coli causes an unexpected reduction in the concentration of the full-length rne transcript, yet results in a small increase in RNase E protein production. These surprising phenomena are explained in terms of a model in which the degradation of this long and highly labile mRNA commences before elongation of the nascent transcript has been completed. In such circumstances, gene expression can be unusually sensitive to changes in mRNA stability.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: C
authors.initials: C
authors.lastname: Jain
authors.forename: J G
authors.initials: JG
authors.lastname: Belasco
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D004722:Endoribonucleases / Q000096:biosynthesis*; D004794:Enzyme Repression; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D005246:Feedback; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D012333:RNA, Messenger; C039919:RNA, recombinant; D011993:Recombinant Fusion Proteins; D012313:RNA; D004722:Endoribonucleases; C022537:ribonuclease E; D001616:beta-Galactosidase