TY  - JOUR
A1  - Maghami, Mohammad Ghaem
A1  - Dey, Surjendu
A1  - Lenz, Ann-Kathrin
A1  - Höbartner, Claudia
T1  - Repurpsing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling
JF  - Angewandte Chemie, International Edition
N2  - In vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2’,5’-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S RNAs in total cellular RNA.
KW  - Antiviral nucleoside analogues
KW  - in vitro selection
KW  - ribozymes
KW  - site-specific RNA labeling
KW  - tenofovir
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205552
VL  - 59
ER  - 
TY  - INPR
A1  - Scheitl, Carolin P.M.
A1  - Ghaem Maghami, Mohammad
A1  - Lenz, Ann-Kathrin
A1  - Höbartner, Claudia
T1  - Site-specific RNA methylation by a methyltransferase ribozyme
T2  - Nature
N2  - Nearly all classes of coding and non-coding RNA undergo post-transcriptional modification including RNA methylation. Methylated nucleotides belong to the evolutionarily most conserved features of tRNA and rRNA.1,2 Many contemporary methyltransferases use the universal cofactor S-adenosylmethionine (SAM) as methyl group donor. This and other nucleotide-derived cofactors are considered as evolutionary leftovers from an RNA World, in which ribozymes may have catalysed essential metabolic reactions beyond self-replication.3 Chemically diverse ribozymes seem to have been lost in Nature, but may be reconstructed in the laboratory by in vitro selection. Here, we report a methyltransferase ribozyme that catalyses the site-specific installation of 1-methyladenosine (m1A) in a substrate RNA, utilizing O6-methylguanine (m6G) as a small-molecule cofactor. The ribozyme shows a broad RNA sequence scope, as exemplified by site-specific adenosine methylation in tRNAs. This finding provides fundamental insights into RNA’s catalytic abilities, serves a synthetic tool to install m1A in RNA, and may pave the way to in vitro evolution of other methyltransferase and demethylase ribozymes.
KW  - Methyltransferase Ribozyme
KW  - RNA Enzymes
KW  - position-specific installation of m1A in RNA
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218687
ER  -