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Aumiller, V.* ; Graebsch, A. ; Kremmer, E. ; Niessing, D. ; Forstemann, K.*

Drosophila Pur-α binds to trinucleotide-repeat containing cellular RNAs and translocates to the early oocyte.

RNA Biol. 9, 633-643 (2012)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Pur-alpha was identified as a DNA-binding protein with high affinity for the single-stranded PUR-motif (GGN)(n). Bound to DNA, Pur-alpha can both activate and repress transcription. In addition, Pur-alpha binds to RNA and may participate in nuclear RNA export as well as transport of cytoplasmic neuronal mRNP granules. The heritable trinucleotide-repeat expansion disease fragile X associated tremor and ataxia syndrome (FXTAS) leads to interaction of Pur-alpha with mutant, abnormally long r(CGG)(n) stretches, which appears to titrate the protein away from its physiologic mRNA targets into nuclear RNA-protein aggregates. We examined the function of Drosophila Pur-alpha and demonstrate that the protein accumulates in the growing oocyte early in oogenesis. Co-purifying proteins reveal that Pur-alpha is part of transported mRNP complexes, analogous to its reported role in nerve cells. We analyzed the subcellular localization of mutant GFP-Pur-alpha fusion proteins where either nucleic acid binding or dimerization, or both, were prevented. We propose that association with mRNAs occurs in the nucleus and is required for nuclear export of the complex. Furthermore, efficient translocation into the oocyte also requires RNA binding as well as dimerization. RNA binding assays demonstrate that recombinant Drosophila Pur-alpha can bind r(CGG)(4) with higher affinity than previously thought. Related sequences, such as r(CAG)(4) and the consensus sequence of the opa-repeat r(CAG)(3) CAA, can also associate with Pur-alpha in vitro and in vivo. The mRNA target spectrum of Pur-alpha may therefore be larger than previously anticipated.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Drosophila ; Oogenesis ; Pura ; Rna Transport ; Mrnp Assembly ; Polar Cell ; Trinucleotide Repeat Expansion Disease ; Opa-repeat; POSTNATAL BRAIN-DEVELOPMENT; MESSENGER-RNA; MEDIATED NEURODEGENERATION; PROTEIN; TRANSLATION; LOCALIZATION; OOGENESIS; COMPLEXES; INTERACTS; POLARITY
ISSN (print) / ISBN 1547-6286
e-ISSN 1555-8584
Zeitschrift RNA Biology
Quellenangaben Band: 9, Heft: 5, Seiten: 633-643 Artikelnummer: , Supplement: ,
Verlag Landes Bioscience
Begutachtungsstatus Peer reviewed