Adenosine Is Inherently Favored as the Branch-Site RNA Nucleotide in a Structural Context That Resembles Natural RNA Splicing

• Published in: Biochemistry (Easton) Vol. 45; no. 9; pp. 2767 - 2771
• Main Authors: Zelin, Elena, Wang, Yangming, Silverman, Scott K.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.03.2006
• Subjects: Adenosine - chemistry; Adenosine - metabolism; Base Sequence; DNA, Catalytic - chemistry; DNA, Catalytic - metabolism; Models, Biological; Molecular Sequence Data; Nucleotides - chemistry; Purines - chemistry; Purines - metabolism; RNA - chemistry; RNA Splicing; Structure-Activity Relationship; Uridine - chemistry; Uridine - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi052499l

We previously used in vitro selection to identify the 7S11 deoxyribozyme, which catalyzes formation of 2‘,5‘-branched RNA using a branch-site adenosine nucleophile and a 5‘-triphosphate electrophile. An unanswered question is whether the use of branch-site adenosine is inherently preferred or a chance event during the particular selection experiment. Here we have found that deoxyribozymes newly selected to use uridine as the branch-site RNA nucleotide in a structural context that resembles natural RNA splicing instead prefer a branch-site adenosine, although adenosine was never available during the selection itself. Our results support a chemical basis for nature's choice of the branch-site nucleotide, which is almost always adenosine in group II introns and the spliceosome.