{"entity": "researcher", "timestamp": "2026-08-08T16:01:59.024Z", "family": "Babina", "given": "Arianne M", "initials": "AM", "orcid": "0000-0002-4635-8396", "affiliations": ["Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63"}}, "publications": [{"entity": "publication", "iuid": "fd4b4d71ebb544eba77fab8cedca6a01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd4b4d71ebb544eba77fab8cedca6a01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd4b4d71ebb544eba77fab8cedca6a01"}}, "title": "Suppression of the Escherichia coli rnpA49 conditionally lethal phenotype by different compensatory mutations.", "authors": [{"family": "Babina", "given": "Arianne M", "initials": "AM", "orcid": "0000-0002-4635-8396", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63.json"}}, {"family": "Kirsebom", "given": "Leif A", "initials": "LA", "orcid": "0000-0002-5092-512X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e80849a89d0043b0b4daff9804c67332.json"}}, {"family": "Andersson", "given": "Dan I", "initials": "DI", "orcid": "0000-0001-6640-2174", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb.json"}}], "type": "journal article", "published": "2024-07-16", "journal": {"title": "RNA", "issn": "1469-9001", "volume": "30", "issue": "8", "pages": "977-991", "issn-l": "1355-8382"}, "abstract": "RNase P is an essential enzyme found across all domains of life that is responsible for the 5'-end maturation of precursor tRNAs. For decades, numerous studies have sought to elucidate the mechanisms and biochemistry governing RNase P function. However, much remains unknown about the regulation of RNase P expression, the turnover and degradation of the enzyme, and the mechanisms underlying the phenotypes and complementation of specific RNase P mutations, especially in the model bacterium, Escherichia coli In E. coli, the temperature-sensitive (ts) rnpA49 mutation in the protein subunit of RNase P has arguably been one of the most well-studied mutations for examining the enzyme's activity in vivo. Here, we report for the first time naturally occurring temperature-resistant suppressor mutations of E. coli strains carrying the rnpA49 allele. We find that rnpA49 strains can partially compensate the ts defect via gene amplifications of either RNase P subunit (rnpA49 or rnpB) or by the acquisition of loss-of-function mutations in Lon protease or RNase R. Our results agree with previous plasmid overexpression and gene deletion complementation studies, and importantly suggest the involvement of Lon protease in the degradation and/or regulatory pathway(s) of the mutant protein subunit of RNase P. This work offers novel insights into the behavior and complementation of the rnpA49 allele in vivo and provides direction for follow-up studies regarding RNase P regulation and turnover in E. coli.", "doi": "10.1261/rna.079909.123", "pmid": "38688559", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11251521"}, {"db": "pii", "key": "rna.079909.123"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2024-11-27T15:36:05.495Z", "modified": "2024-11-27T15:36:59.692Z"}, {"entity": "publication", "iuid": "7c0db5cdb6844734a45a079ac25ca47b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c0db5cdb6844734a45a079ac25ca47b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c0db5cdb6844734a45a079ac25ca47b"}}, "title": "A novel type of colistin resistance genes selected from random sequence space.", "authors": [{"family": "Knopp", "given": "Michael", "initials": "M", "orcid": "0000-0002-8218-3263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e.json"}}, {"family": "Babina", "given": "Arianne M", "initials": "AM", "orcid": "0000-0002-4635-8396", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63.json"}}, {"family": "Gudmundsd\u00f3ttir", "given": "J\u00f3n\u00edna S", "initials": "JS", "orcid": "0000-0002-4500-4078", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd10ee75400d497a8d1c5b9ac7fccdc7.json"}}, {"family": "Douglass", "given": "Martin V", "initials": "MV"}, {"family": "Trent", "given": "M Stephen", "initials": "MS", "orcid": "0000-0001-6134-1800", "researcher": {"href": "https://publications.scilifelab.se/researcher/009aef5966e64414a03b8bb67351dff8.json"}}, {"family": "Andersson", "given": "Dan I", "initials": "DI", "orcid": "0000-0001-6640-2174", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "17", "issue": "1", "pages": "e1009227", "issn-l": "1553-7390"}, "abstract": "Antibiotic resistance is a rapidly increasing medical problem that severely limits the success of antibiotic treatments, and the identification of resistance determinants is key for surveillance and control of resistance dissemination. Horizontal transfer is the dominant mechanism for spread of resistance genes between bacteria but little is known about the original emergence of resistance genes. Here, we examined experimentally if random sequences can generate novel antibiotic resistance determinants de novo. By utilizing highly diverse expression libraries encoding random sequences to select for open reading frames that confer resistance to the last-resort antibiotic colistin in Escherichia coli, six de novo colistin resistance conferring peptides (Dcr) were identified. The peptides act via direct interactions with the sensor kinase PmrB (also termed BasS in E. coli), causing an activation of the PmrAB two-component system (TCS), modification of the lipid A domain of lipopolysaccharide and subsequent colistin resistance. This kinase-activation was extended to other TCS by generation of chimeric sensor kinases. Our results demonstrate that peptides with novel activities mediated via specific peptide-protein interactions in the transmembrane domain of a sensory transducer can be selected de novo, suggesting that the origination of such peptides from non-coding regions is conceivable. In addition, we identified a novel class of resistance determinants for a key antibiotic that is used as a last resort treatment for several significant pathogens. The high-level resistance provided at low expression levels, absence of significant growth defects and the functionality of Dcr peptides across different genera suggest that this class of peptides could potentially evolve as bona fide resistance determinants in natura.", "doi": "10.1371/journal.pgen.1009227", "pmid": "33411736", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7790251"}, {"db": "pii", "key": "PGENETICS-D-20-01241"}], "notes": [], "created": "2023-03-07T14:36:24.716Z", "modified": "2024-01-16T13:46:30.935Z"}]}