Transliteration of synthetic genetic enzymes.
Nucleic Acids Res
; 49(20): 11438-11446, 2021 11 18.
Article
in En
| MEDLINE
| ID: mdl-34634814
ABSTRACT
Functional nucleic acids lose activity when their sequence is prepared in the backbone architecture of a different genetic polymer. The only known exception to this rule is a subset of aptamers whose binding mechanism involves G-quadruplex formation. We refer to such examples as transliteration-a synthetic biology concept describing cases in which the phenotype of a nucleic acid molecule is retained when the genotype is written in a different genetic language. Here, we extend the concept of transliteration to include nucleic acid enzymes (XNAzymes) that mediate site-specific cleavage of an RNA substrate. We show that an in vitro selected 2'-fluoroarabino nucleic acid (FANA) enzyme retains catalytic activity when its sequence is prepared as α-l-threofuranosyl nucleic acid (TNA), and vice versa, a TNA enzyme that remains functional when its sequence is prepared as FANA. Structure probing with DMS supports the hypothesis that FANA and TNA enzymes having the same primary sequence can adopt similarly folded tertiary structures. These findings provide new insight into the sequence-structure-function paradigm governing biopolymer folding.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nucleic Acids
/
Enzymes
Language:
En
Journal:
Nucleic Acids Res
Year:
2021
Document type:
Article
Affiliation country:
China