Bidirectional effectors of a group I intron ribozyme

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The group I self-splicing introns found in many organisms are competitively inhibited by L-arginine. We have found thatL-arginine acts stereoselectively on the Pc1.LSU nuclear group I intron of Pneumocystis carinil, competitively inhibiting the first (cleavage) step of the splicing reaction and stimulating the second (ligation) step. Stimulation of the second step is most clearly demonstrated in reactions whose first step is blocked after 15 min by addition of pentamidine. The guanidine moiety of arginine is required for both effects. L-Canavanine is a more potent inhibitor than L-arginine yet it falls to stimulate. L-Arginine derivatized on its carboxyl group as an amide, ester or peptide is more potent than L-arginine as a stimulator and inhibitor, with di-arginine amide and tri-arginine being the most potent effectors tested. The most potent peptides tested are 10 000 times as effective as L-arginine in inhibiting ribozyme activity, and nearly 400 times as effective as stimulators. Arginine and some of its derivatives apparently bind to site(s) on the ribozyme to alter its conformation to one more active in the second step of splicing while competing with guanosine substrate in the first step. This phenomenon indicates that ribozymes, like protein enzymes, can be inhibited or stimulated by non-substrate low molecular weight compounds, which suggests that such compounds may be developed as pharmacological agents actingon RNA targets.

Original languageEnglish (US)
Pages (from-to)1284-1291
Number of pages8
JournalNucleic Acids Research
Volume23
Issue number8
DOIs
StatePublished - Apr 25 1995
Externally publishedYes

Fingerprint

Catalytic RNA
Arginine
Introns
Peptides
Inhibitor
Conformation
Enzymes
Substrate
Protein
Derivative
Target
Amides
Canavanine
Pneumocystis
GIR1 ribozyme
Pentamidine
Guanosine
Guanidine
RNA
Ligation

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)
  • Genetics

Cite this

Bidirectional effectors of a group I intron ribozyme. / Liu, Yong; Leibowitz, Michael J.

In: Nucleic Acids Research, Vol. 23, No. 8, 25.04.1995, p. 1284-1291.

Research output: Contribution to journalArticle

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