Evidence for instability of mRNAs containing AUUUA motifs mediated through translation-dependent assembly of a > 20S degradation complex.

Abstract:

:Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most clearly true for granulocyte monocyte colony stimulating factor (GM-CSF) mRNA whose AUUUA motifs are conserved phylogenetically and whose presence in an otherwise stable beta-globin mRNA results in a 50-fold decrease in accumulated mRNA level. We show that RNA instability conferred by the GM-CSF AU motif requires the mRNA to be actively translated and the AU motif to be within the 3'-untranslated region. By analysis of the sedimentation characteristics, we identify a large (> 20S), divalent cation-independent complex found only on unstable RNAs. Like instability, complex formation (1) is dependent on translation of the RNA, (2) requires intact AUUUA motifs, and (3) is blocked by ribosome translocation across the AU-rich motif. We propose that RNA instability mediated by the AU motif is achieved through translation-dependent assembly of this large mRNA-destabilizing complex.

journal_name

Genes Dev

journal_title

Genes & development

authors

Savant-Bhonsale S,Cleveland DW

doi

10.1101/gad.6.10.1927

subject

Has Abstract

pub_date

1992-10-01 00:00:00

pages

1927-39

issue

10

eissn

0890-9369

issn

1549-5477

journal_volume

6

pub_type

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