Sequence-Specific Installation of Aryl Groups in RNA via DNA-Catalyst Conjugates
Abstract
Installing functional groups at specific sites in existing RNA molecules remains a challenge for modification, labeling, and therapeutic strategies. Here we describe the use of DNA oligonucleotides carrying a catalytic amine group to effect the aqueous S N Ar arylation of 2'-OH groups at sequence-complementary sites in RNAs. Chloro-pyrimidine electrophiles are shown to react with amino-DNA conjugates, resulting in a proposed transient ammonium aryl intermediate that can react with RNA near the DNA binding site, delivering the heterocycle to the RNA in high yields. In a test of utility, we construct an aryl electrophile carrying an azide group, and apply this strategy to fluorescently label messenger RNAs locally at the polyA tail. We also employ the approach to direct in vitro arylation in the coding region of a messenger RNA, knocking down protein expression selectively in the presence of another coding RNA. This sequence-directed catalytic strategy enables multiple applications in RNA labeling and modification.
Read the paper
Related studies
- Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts
- For a Healthy Histone Code, a Little SUMO in the Tail Keeps the Acetyl Away
- Discovering a binary CTCF code with a little help from BORIS
- Article Commentary: Stabilizing the Code–-Methods to Preserve RNA Prove Their Worth
- Foreword to the Special Issue for the RINTC (The Implicit Seismic Risk of Code-Conforming Structures) Project
- Commentary: Promoting Health and Well-being in Pediatric Primary Care Settings: Using Health and Behavior Codes at Routine Well-child Visits
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.