U-to-C RNA editing by synthetic PPR-DYW proteins in bacteria and human culture cells

Mizuho Ichinose, Masuyo Kawabata, Yumi Akaiwa, Yasuka Shimajiri, Izumi Nakamura, Takayuki Tamai, Takahiro Nakamura, Yusuke Yagi, Bernard Gutmann

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Programmable RNA editing offers significant therapeutic potential for a wide range of genetic diseases. Currently, several deaminase enzymes, including ADAR and APOBEC, can perform programmable adenosine-to-inosine or cytidine-to-uridine RNA correction. However, enzymes to perform guanosine-to-adenosine and uridine-to-cytidine (U-to-C) editing are still lacking to complete the set of transition reactions. It is believed that the DYW:KP proteins, specific to seedless plants, catalyze the U-to-C reactions in mitochondria and chloroplasts. In this study, we designed seven DYW:KP domains based on consensus sequences and fused them to a designer RNA-binding pentatricopeptide repeat (PPR) domain. We show that three of these PPR-DYW:KP proteins edit targeted uridine to cytidine in bacteria and human cells. In addition, we show that these proteins have a 5′ but not apparent 3′ preference for neighboring nucleotides. Our results establish the DYW:KP aminase domain as a potential candidate for the development of a U-to-C editing tool in human cells.

Original languageEnglish
Article number968
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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