Programmed cell death by hok/sok of plasmid R1: Processing at the hok mRNA 3'-end triggers structural rearrangements that allow translation and antisense RNA binding

AP Gultyaev, T Franch, K Gerdes

79 Citationer (Scopus)

Abstract

The hok/sok locus of plasmid R1 mediates plasmid stabilization by killing of plasmid-free cells. The locus specifies two RNAs, hok mRNA and Sok antisense RNA. The post-segregational killing mediated by hok/sok is governed by a complicated control mechanism that involves both post-transcriptional inhibition of translation by Sok-RNA and activation of hok translation by mRNA 3' processing. Sok-RNA inhibits translation of a reading frame (mok) that overlaps with hok, and translation of hok is coupled to translation of mok. In the inactive full-length hok mRNA, the translational activator element at the mRNA 5'-end (tac) is sequestered by the fold-back-inhibitory element located at the mRNA 3'-end (fbi). The 5' to 3' pairing locks the RNA in an inert configuration in which the SDmok and Sok-RNA target regions are sequestered. Here we show that the 3' processing leads to major structural rearrangements in the mRNA 5'-end. The structure of the refolded RNA explains activation of translation and antisense RNA binding. The refolded RNA contains an antisense RNA target stem-loop that presents the target nucleotides in a single-stranded conformation. The stem of the target hairpin contains SDmok and AUG(mok) in a paired configuration. Using toeprinting analysis, we show that this pairing keeps SDmok in an accessible configuration. Furthermore, a mutational analysis shows that an internal loop in the target stem is prerequisite for efficient translation and antisense RNA binding. (C) 1997 Academic Press Limited.
OriginalsprogEngelsk
TidsskriftJournal of Molecular Biology
Vol/bind273
Udgave nummer1
Sider (fra-til)26-37
Antal sider12
ISSN0022-2836
DOI
StatusUdgivet - 1997
Udgivet eksterntJa

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