Site-specific cleavage of RNAs derived from the PIM1 3′-UTR by a metal-free artificial ribonuclease

  • Oligonucleotide conjugates of tris(2-aminobenzimidazole) have been reported previously to cleave complementary RNA strands with high levels of sequence and site specificity. The RNA substrates used in these studies were oligonucleotides not longer than 29-mers. Here we show that ~150–400-mer model transcripts derived from the 3′-untranslated region of the PIM1 mRNA reacted with rates and specificities comparable to those of short oligonucleotide substrates. The replacement of DNA by DNA/LNA mixmers further increased the cleavage rate. Tris(2-aminobenzimidazoles) were designed to interact with phosphates and phosphate esters. A cell, however, contains large amounts of phosphorylated species that may cause competitive inhibition of RNA cleavage. It is thus important to note that no loss in reaction rates was observed in phosphate buffer. This opens the way to in-cell applications for this type of artificial nuclease. Furthermore, we disclose a new synthetic method giving access to tris(2-aminobenzimidazoles) in multigram amounts.

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Author:Felix Zellmann, Laura Thomas, Ute Scheffer, Roland K. Hartmann, Michael GöbelORCiDGND
Pubmed Id:
Parent Title (English):Molecules
Place of publication:Basel
Contributor(s):Roger Strömberg
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/02/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/11
Tag:2-aminobenzimidazole; DNA/LNA mixmers; cleavage of large RNA molecules; cleavage site selection; dye labeling; guanidine analogs; oligonucleotides; specificity of cleavage
Issue:4, Art. 807
Page Number:11
First Page:1
Last Page:11
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Open-Access-Publikationsfonds:Biochemie, Chemie und Pharmazie
Licence (German):License LogoCreative Commons - Namensnennung 4.0