Developmental RNA processing of 3'UTRs in Hox mRNAs as a context-dependent mechanism modulating visibility to microRNAs

Thomsen, Stefan, Azzam, Ghows, Kaschula, Richard, Williams, Lucy S. and Alonso, Claudio R. (2010) Developmental RNA processing of 3'UTRs in Hox mRNAs as a context-dependent mechanism modulating visibility to microRNAs. Development, 137 (17). pp. 2951-2960. ISSN 1011-6370

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The Drosophila Hox gene Ultrabithorax (Ubx) controls the development of thoracic and abdominal segments, allocating segment-specific features to different cell lineages. Recent studies have shown that Ubx expression is post-transcriptionally regulated by two microRNAs (miRNAs), miR-iab4 and miR-iab8, acting on target sites located in the 3' untranslated regions (UTRs) of Ubx mRNAs. Here, we show that during embryonic development Ubx produces mRNAs with variable 3'UTRs in different regions of the embryo. Analysis of the resulting remodelled 3'UTRs shows that each species harbours different sets of miRNA target sites, converting each class of Ubx mRNA into a considerably different substrate for miRNA regulation. Furthermore, we show that the distinct developmental distributions of Ubx 3'UTRs are established by a mechanism that is independent of miRNA regulation and therefore are not the consequence of miR-iab4/8-mediated RNA degradation acting on those sensitive mRNA species; instead, we propose that this is a hard-wired 3'UTR processing system that is able to regulate target mRNA visibility to miRNAs according to developmental context. We show that reporter constructs that include Ubx short and long 3'UTR sequences display differential expression within the embryonic central nervous system, and also demonstrate that mRNAs of three other Hox genes suffer similar and synchronous developmental 3'UTR processing events during embryogenesis. Our work thus reveals that developmental RNA processing of 3'UTR sequences is a general molecular strategy used by a key family of developmental regulators so that their transcripts can display different levels of visibility to miRNA regulation according to developmental cues.

Item Type: Article
Additional Information: [***RECOMMENDED by the Faculty of 1000 Biology, see McDougall C, Degnan B: 2010.***] [With "In this issue" highlight comment in Development 137 (17)]
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science
Depositing User: Stefan Thomsen
Date Deposited: 06 Feb 2012 20:47
Last Modified: 19 Jun 2013 10:13
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