A conserved motif controls nuclear localization of Drosophila Muscleblind

Molecules and Cells
Juan M Fernandez-Costa, Ruben Artero

Abstract

Human Muscleblind-like proteins are alternative splicing regulators that are functionally altered in the RNA-mediated disease myotonic dystrophy. There are different Muscleblind protein isoforms in Drosophila and we previously determined that these have different subcellular localizations in the COS-M6 cell line. Here, we describe the conservation of the sequence motif KRAEK in isoforms C and E and propose a specific function for this motif. Different Muscleblind isoforms localize to the peri-plasma membrane (MblA), cytoplasm (MblB), or show no preference for the nuclear or cytoplasmic compartment (MblC and MblD) in Drosophila S2 cells transiently transfected with Musclebind expression plasmids. Mutation of the KRAEK motif reduces MblC nuclear localization, whereas fusion of a single KRAEK motif to the heterologous protein beta-galactosidase is sufficient to target the reporter protein to the nucleus of S2 cells. This motif is not exclusive to Muscleblind proteins and is detected in several other protein types. Taken together, these results suggest that the KRAEK motif regulates nuclear translocation of Muscleblind and may constitute a new class of nuclear localization signal.

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Citations

Apr 15, 2011·Biological Reviews of the Cambridge Philosophical Society·Juan M Fernandez-CostaRuben Artero
Sep 4, 2014·Nucleic Acids Research·Patryk KoniecznyKrzysztof Sobczak
Feb 4, 2016·International Journal of Molecular Sciences·Bo-Wen ZhangHong Chen
Dec 3, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Feihu WangFang Jin
Dec 3, 2016·Nucleic Acids Research·Patryk KoniecznyKrzysztof Sobczak
Sep 28, 2017·RNA Biology·Patryk KoniecznyKrzysztof Sobczak

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