Global regulators orchestrate group II intron retromobility.
Group II introns are hypothesized to share common ancestry with both nuclear spliceosomal introns and retrotransposons, which collectively occupy the majority of genome space in higher eukaryotes. These phylogenetically diverse introns are mobile retroelements that move through an RNA intermediate. Disruption of Escherichia coli genes encoding enzymes that catalyze synthesis of global regulators cAMP and ppGpp inhibits group II intron retromobility. These small molecules program genetic transitions between nutrient excess and starvation. Accordingly, we demonstrated that glucose depletion of wild-type cells and cAMP supplementation of mutants stimulated retromobility. Likewise, amino acid starvation, which induces the alarmone ppGpp, activated retromobility. In both cases, retrotransposition to ectopic sites was favored over retrohoming. Interestingly, these stimulatory effects are mediated at the level of the DNA target, rather than of expression of the retroelement. Thereby, during metabolic stress, cAMP and ppGpp control group II intron movement in concert with the cell's global genetic circuitry, stimulating genetic diversity.
Coros
Colin J
CJ
Wadsworth Center, New York State Department of Health, Center for Medical Sciences, 150 New Scotland Avenue, Albany, NY 12208, USA.
Piazza
Carol Lyn
CL
Chalamcharla
Venkata R
VR
Smith
Dorie
D
Belfort
Marlene
M
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D002876:Chromosomes, Bacterial; D000242:Cyclic AMP / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006159:Guanosine Tetraphosphate / Q000502:physiology*; D007438:Introns / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000378:metabolism; D018626:Retroelements / Q000235:genetics / Q000502:physiology*
D000596:Amino Acids; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D018626:Retroelements; D006159:Guanosine Tetraphosphate; D000242:Cyclic AMP; C027627:guanosine-3',5'-bis(diphosphate) 3'-pyrophosphatase; D011755:Pyrophosphatases; D000262:Adenylyl Cyclases