Publikationsdatum:
2010-10-19
Beschreibung:
Piwi-associated RNAs (piRNAs), a specific class of 24- to 30-nucleotide-long RNAs produced by the Piwi-type of Argonaute proteins, have a specific germline function in repressing transposable elements. This repression is thought to involve heterochromatin formation and transcriptional and post-transcriptional silencing. The piRNA pathway has other essential functions in germline stem cell maintenance and in maintaining germline DNA integrity. Here we uncover an unexpected function of the piRNA pathway in the decay of maternal messenger RNAs and in translational repression in the early embryo. A subset of maternal mRNAs is degraded in the embryo at the maternal-to-zygotic transition. In Drosophila, maternal mRNA degradation depends on the RNA-binding protein Smaug and the deadenylase CCR4, as well as the zygotic expression of a microRNA cluster. Using mRNA encoding the embryonic posterior morphogen Nanos (Nos) as a paradigm to study maternal mRNA decay, we found that CCR4-mediated deadenylation of nos depends on components of the piRNA pathway including piRNAs complementary to a specific region in the nos 3' untranslated region. Reduced deadenylation when piRNA-induced regulation is impaired correlates with nos mRNA stabilization and translational derepression in the embryo, resulting in head development defects. Aubergine, one of the Argonaute proteins in the piRNA pathway, is present in a complex with Smaug, CCR4, nos mRNA and piRNAs that target the nos 3' untranslated region, in the bulk of the embryo. We propose that piRNAs and their associated proteins act together with Smaug to recruit the CCR4 deadenylation complex to specific mRNAs, thus promoting their decay. Because the piRNAs involved in this regulation are produced from transposable elements, this identifies a direct developmental function for transposable elements in the regulation of gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rouget, Christel -- Papin, Catherine -- Boureux, Anthony -- Meunier, Anne-Cecile -- Franco, Benedicte -- Robine, Nicolas -- Lai, Eric C -- Pelisson, Alain -- Simonelig, Martine -- R01 GM083300/GM/NIGMS NIH HHS/ -- R01-GM083300/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Oct 28;467(7319):1128-32. doi: 10.1038/nature09465. Epub 2010 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉mRNA Regulation and Development, Institute of Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, Cedex 5, 34396 Montpellier, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20953170" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
3' Untranslated Regions/genetics
;
Animals
;
Argonaute Proteins
;
Cytoplasm/genetics/metabolism
;
DNA Transposable Elements/genetics
;
Drosophila Proteins/genetics/metabolism
;
Drosophila melanogaster/cytology/*embryology/*genetics
;
Embryo, Nonmammalian/cytology/embryology/metabolism
;
Female
;
*Gene Expression Regulation, Developmental
;
Mothers
;
Peptide Initiation Factors/genetics/metabolism
;
Polyadenylation/*genetics
;
*RNA Stability
;
RNA, Messenger/genetics/*metabolism
;
RNA, Small Interfering/*genetics/metabolism
;
RNA-Binding Proteins/genetics/metabolism
;
Repressor Proteins/genetics/metabolism
;
Ribonucleases/genetics/metabolism
;
Zygote/metabolism
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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