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Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity

By Marcos De la Peña, Selma Gago and Ricardo Flores

Abstract

Natural hammerhead ribozymes are mostly found in some viroid and viroid-like RNAs and catalyze their cis cleavage during replication. Hammerheads have been manipulated to act in trans and assumed to have a similar catalytic behavior in this artificial context. However, we show here that two natural cis-acting hammerheads self-cleave much faster than trans-acting derivatives and other reported artificial hammerheads. Moreover, modifications of the peripheral loops 1 and 2 of one of these natural hammerheads induced a >100-fold reduction of the self-cleavage constant, whereas engineering a trans-acting artificial hammerhead into a cis derivative by introducing a loop 1 had no effect. These data show that regions external to the central conserved core of natural hammerheads play a role in catalysis, and suggest the existence of tertiary interactions between these peripheral regions. The interactions, determined by the sequence and size of loops 1 and 2 and most likely of helices I and II, must result from natural selection and should be studied in order to better understand the hammerhead requirements in vivo

Topics: Articles
Publisher: Oxford University Press
Year: 2003
DOI identifier: 10.1093/emboj/cdg530
OAI identifier: oai:pubmedcentral.nih.gov:213784
Provided by: PubMed Central
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