Event
Ribozymes meet RNA modifications| Title of the event | Ribozymes meet RNA modifications |
| Series | Fassberg Seminar - ONLINE SEMINAR |
| Organizer | Max-Planck-Institut für biophysikalische Chemie (MPIBPC) |
| Speaker | Claudia Höbartner |
| Speaker institution | Institute of Organic Chemistry, Julius Maximilians University Würzburg |
| Type of event | Seminar |
| Category | Forschung |
| Registration required | Nein |
| Details | Nearly all classes of RNA are decorated with post-transcriptional modifications, which play important functional roles in all kingdoms of life. Methylated nucleotides belong to the most evolutionary conserved RNA modifications that could have influenced the evolutionary path of catalytic RNA. Primordial ribozymes may have installed modifications to enhance catalysis, or mediated their removal to facilitate replication and storage of genetic information. In vitro evolution in the laboratory offers the possibility to reconstruct analogues of such potentially extinct ribozymes. Using in vitro selection from random nucleic acid libraries, we identified RNA-cleaving DNA enzymes that specifically recognize modified adenosines, including N6-methyl-adenosine (m6A) and N6-isopentenyladenosine (i6A), and strongly discriminate modified from unmodified RNA.[1] To find nucleic acid enzymes that install RNA modifications, we took advantage of a selection strategy that resulted in ribozymes for RNA-catalysed labelling of RNA, by attachment of fluorescent ATP or re-purposed antiviral nucleotide analogues at internal ribose hydroxyl groups.[2] We followed a similar route to enrich RNAs that catalyse the site-specific installation of RNA modifications on the nucleobase. This presentation will discuss the recently discovered methyltransferase ribozyme that catalyses the site-specific installation of 1-methyl¬adenosine (m1A) in a substrate RNA, utilizing O6-methylguanine (m6G) as a small-molecule cofactor.[3] The ribozyme shows a broad RNA sequence scope, as exemplified by site-specific adenosine methylation in tRNAs. These findings provide fundamental insights into RNA’s catalytic abilities, serve synthetic tools to install m1A in RNA, and may pave the way to in vitro evolution of other methyltransferase and demethylase ribozymes. References [1] a) Sednev MV, Mykhailiuk V, Choudhury P, Halang J, Sloan KE, Bohnsack MT, Höbartner C. N6‐Methyladenosine‐sensitive RNA‐cleaving deoxyribozymes. Angew Chem Int Ed 2018, 57, 15117-15121. b) Liaqat A, Stiller C, Michel M, Sednev MV, Höbartner C. N6-Isopentenyladenosine in RNA determines the cleavage site of endonuclease deoxyribozymes. Angew Chem Int Ed 2020, 59, 18627-18631. [2] a) Ghaem Maghami M, Scheitl CPM, Höbartner C. Direct in vitro selection of trans-acting ribozymes for posttranscriptional, site-specific, and covalent fluorescent labeling of RNA. J Am Chem Soc 2019, 141, 19546–19549. b) Ghaem Maghami M, Dey S, Lenz A-K, Höbartner C. Repurposing antiviral drugs for orthogonal RNA-catalyzed labeling of RNA. Angew Chem Int Ed 2020 59, 9335-9339. [3] Scheitl CPM, Ghaem Maghami M, Lenz A-K, Höbartner C. Site-specific RNA methylation by a methyltransferase ribozyme. Nature 2020, 587, 663-667. |
| Date | Start: 01.04.2021, 11:00 Uhr Ende: 01.04.2021 , 12:00 Uhr |
| Location |
Max-Planck-Institut für biophysikalische Chemie (MPIBPC) (Am Faßberg 11) Zoom Online Seminar |
| Contact |
05512012010 gd.office@mpibpc.mpg.de |
| File attachment | Fassberg_Announcement_C_Höbartner.pdf |