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Development, Cellular Neuroscience, Gene Expression, Molecular Neuroscience
Abstract:
In mammalian neurons, targeting and translation of specific mRNAs in dendrites contribute to synaptic
plasticity. After nuclear export, mRNAs designated for dendritic transport are generally assumed to be
translationally dormant and activity of individual synapses may locally trigger their extrasomatic
translation. We show that the long, GC-rich 59-untranslated region of dendritic SAPAP3 mRNA restricts
translation initiation via a mechanism that involves an upstream open reading frame (uORF). In addition,
the uORF enables the use of an alternative translation start site, permitting synthesis of two SAPAP3
isoforms from a single mRNA. While both isoforms progressively accumulate at postsynaptic densities
during early rat brain development, their levels relative to each other vary in different adult rat brain areas.
Thus, alternative translation initiation events appear to regulate relative expression of distinct SAPAP3
isoforms in different brain regions, which may function to influence synaptic plasticity.
