7QP2

1-deazaguanosine modified-RNA Sarcin Ricin Loop

Summary for 7QP2

• Entry DOI: 10.2210/pdb7qp2/pdb
• Descriptor: RNA (27-MER), GLYCEROL (3 entities in total)
• Functional Keywords: modified-rna, rna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 8835.36

Authors

Ennifar, E.,Micura, R.,Bereiter, R.,Renard, E.,Kreutz, C. (deposition date: 2021-12-30, release date: 2022-07-20, Last modification date: 2024-01-31)

Primary citation

Bereiter, R.,Renard, E.,Breuker, K.,Kreutz, C.,Ennifar, E.,Micura, R.
1-Deazaguanosine-Modified RNA: The Missing Piece for Functional RNA Atomic Mutagenesis.
J.Am.Chem.Soc., 144:10344-10352, 2022

PubMed Abstract: Atomic mutagenesis is the key to advance our understanding of RNA recognition and RNA catalysis. To this end, deazanucleosides are utilized to evaluate the participation of specific atoms in these processes. One of the remaining challenges is access to RNA-containing 1-deazaguanosine (cG). Here, we present the synthesis of this nucleoside and its phosphoramidite, allowing first time access to cG-modified RNA. Thermodynamic analyses revealed the base pairing parameters for cG-modified RNA. Furthermore, by NMR spectroscopy, a cG-triggered switch of Watson-Crick into Hoogsteen pairing in HIV-2 TAR RNA was identified. Additionally, using X-ray structure analysis, a guanine-phosphate backbone interaction affecting RNA fold stability was characterized, and finally, the critical impact of an active-site guanine in twister ribozyme on the phosphodiester cleavage was revealed. Taken together, our study lays the synthetic basis for cG-modified RNA and demonstrates the power of the completed deazanucleoside toolbox for RNA atomic mutagenesis needed to achieve in-depth understanding of RNA recognition and catalysis.

PubMed: 35666572
DOI: 10.1021/jacs.2c01877

Experimental method

X-RAY DIFFRACTION (0.9 Å)