Metal ion catalysis during splicing of premessenger RNA

Erik J. Sontheimer, Sengen Sun and Joseph A. Piccirilli ()
Additional contact information
Erik J. Sontheimer: Howard Hughes Medical Institute, The University of Chicago
Sengen Sun: Howard Hughes Medical Institute, The University of Chicago
Joseph A. Piccirilli: Howard Hughes Medical Institute, The University of Chicago

Nature, 1997, vol. 388, issue 6644, 801-805

Abstract: Abstract The removal of intervening sequences from premessenger RNA is essential for the expression of most eukaryotic genes. The spliceosome ribonucleoprotein complex catalyses intron removal by two sequential phosphotransesterification reactions1, but the catalytic mechanisms are unknown. It has been proposed that two divalent metal ions may mediate catalysis of both reaction steps, activating the 2′- or 3′-hydroxyl groups for nucleophilic attack and stabilizing the 3′-oxyanion leaving groups by direct coordination2. Here we show that in splicing reactions with a precursor RNA containing a 3′-sulphur substitution at the 5′ splice site, interaction between metal ion and leaving group is essential for catalysis of the first reaction step. This establishes that the spliceosome is a metalloenzyme and demonstrates a direct parallel with the catalytic strategy used by the self-splicing group I intron from Tetrahymena3. In contrast, 3′-sulphur substitution at the 3′ splice site provides no evidence for a metal ion–leaving group interaction in the second reaction step, suggesting that the two steps of splicing proceed by different catalytic mechanisms and therefore in distinct active sites.

Date: 1997
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/42068 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:388:y:1997:i:6644:d:10.1038_42068

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/42068

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().