RRC ID |
82099
|
Author |
Ichinose M, Kawabata M, Akaiwa Y, Shimajiri Y, Nakamura I, Tamai T, Nakamura T, Yagi Y, Gutmann B.
|
Title |
U-to-C RNA editing by synthetic PPR-DYW proteins in bacteria and human culture cells.
|
Journal |
Commun Biol
|
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.
|
Volume |
5(1)
|
Pages |
968
|
Published |
2022-9-15
|
DOI |
10.1038/s42003-022-03927-3
|
PII |
10.1038/s42003-022-03927-3
|
PMID |
36109586
|
PMC |
PMC9478123
|
MeSH |
Adenosine / metabolism
Bacteria / genetics
Bacteria / metabolism
Cytidine* / genetics
Cytidine* / metabolism
Guanosine / metabolism
Humans
Inosine
Nucleotides / metabolism
Plant Proteins / genetics
RNA / metabolism
RNA Editing*
Uridine / metabolism
|
Resource |
Human and Animal Cells |
293T(RCB2202) |