QNQKE targeting motif for the SMN-Gemin multiprotein complexin neurons.

Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly-(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.