PABP and the poly(A) tail augment microRNA repression by facilitated miRISC binding

Polyadenylated mRNAs are typically more strongly repressed by microRNAs (miRNAs) than their nonadenylated counterparts. Using a Drosophila melanogaster cell-free translation system, we found that this effect is mediated by the poly(A)-binding protein (PABP). miRNA repression was positively correlate...

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Hauptverfasser: Moretti, Francesca (VerfasserIn) , Hentze, Matthias W. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 2012
In: Nature structural & molecular biology
Year: 2012, Jahrgang: 19, Heft: 6, Pages: 603-608
ISSN:1545-9985
DOI:10.1038/nsmb.2309
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1038/nsmb.2309
Verlag, Volltext: https://www.nature.com/articles/nsmb.2309
Volltext
Verfasserangaben:Francesca Moretti, Constanze Kaiser, Agnieszka Zdanowicz-Specht, Matthias W. Hentze
Beschreibung
Zusammenfassung:Polyadenylated mRNAs are typically more strongly repressed by microRNAs (miRNAs) than their nonadenylated counterparts. Using a Drosophila melanogaster cell-free translation system, we found that this effect is mediated by the poly(A)-binding protein (PABP). miRNA repression was positively correlated with poly(A) tail length, but this stimulatory effect on repression was lost when translation was repressed by the tethered GW182 silencing domain rather than the miRNA-induced silencing complex (miRISC) itself. These findings are mechanistically explained by a notable function of PABP: it promotes association of miRISC with miRNA-regulated mRNAs. We also found that PABP association with mRNA rapidly diminished with miRISC recruitment and before detectable deadenylation. We integrated these data into a revised model for the function of PABP and the poly(A) tail in miRNA-mediated translational repression.
Beschreibung:Gesehen am 09.10.2018
Beschreibung:Online Resource
ISSN:1545-9985
DOI:10.1038/nsmb.2309