Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation

被引:13
作者
Chua, John Jia En [1 ]
Schob, Claudia [1 ]
Rehbein, Monika [1 ]
Gkogkas, Christos G. [3 ]
Richter, Dietmar [2 ]
Kindler, Stefan [1 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany
[2] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol, D-20246 Hamburg, Germany
[3] Rosalind & Morris Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada
关键词
OPEN READING FRAMES; DENDRITIC TARGETING ELEMENT; RAT-BRAIN; DEPENDENT TRANSLATION; INTERNAL INITIATION; SYNAPTIC PLASTICITY; PROTEIN-SYNTHESIS; REINITIATION; EXPRESSION; LOCALIZATION;
D O I
10.1038/srep00484
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 5'-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.
引用
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页数:10
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NATURE NEUROSCIENCE, 2007, 10 (05) :578-587