Translation efficiency affects the sequence-independent +1 ribosomal frameshifting by polyamines.

Abstract:

:Antizyme (AZ) interacts with ornithine decarboxylase, which catalyzes the first step of polyamine biosynthesis and recruits it to the proteasome for degradation. Synthesizing the functional AZ protein requires transition of the reading frame at the termination codon. This programmed +1 ribosomal frameshifting is induced by polyamines, but the molecular mechanism is still unknown. In this study, we explored the mechanism of polyamine-dependent +1 frameshifting using a human cell-free translation system. Unexpectedly, spermidine induced +1 frameshifting in the mutants replacing the termination codon at the shift site with a sense codon. Truncation experiments showed that +1 frameshifting occurred promiscuously in various positions of the AZ sequence. The probability of this sequence-independent +1 frameshifting increased in proportion to the length of the open reading frame. Furthermore, the +1 frameshifting was induced in some sequences other than the AZ gene in a polyamine-dependent manner. These findings suggest that polyamines have the potential to shift the reading frame in the +1 direction in any sequence. Finally, we showed that the probability of the sequence-independent +1 frameshifting by polyamines is likely inversely correlated with translation efficiency. Based on these results, we propose a model of the molecular mechanism for AZ +1 frameshifting.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Oguro A,Shigeta T,Machida K,Suzuki T,Iwamoto T,Matsufuji S,Imataka H

doi

10.1093/jb/mvaa032

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

139-149

issue

2

eissn

0021-924X

issn

1756-2651

pii

5809147

journal_volume

168

pub_type

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