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

研究成果: ジャーナルへの寄稿学術誌査読

16 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号968
ジャーナルCommunications Biology
5
1
DOI
出版ステータス出版済み - 12月 2022

!!!All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 生化学、遺伝学、分子生物学一般
  • 農業および生物科学一般

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