Activity-dependent polyadenylation in neurons
Program in Molecular Medicine
Animals; Brain Chemistry; Cells, Cultured; Gene Library; Mice; Neurons; Oligonucleotide Array Sequence Analysis; Oocytes; Polyadenylation; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA-Binding Proteins; Rats; Xenopus
Life Sciences | Medicine and Health Sciences
Activity-dependent changes in protein synthesis modify synaptic efficacy. One mechanism that regulates mRNA translation in the synapto-dendritic compartment is cytoplasmic polyadenylation, a process controlled by CPEB, the cytoplasmic polyadenylation element (CPE)-specific RNA binding protein. In neurons, very few mRNAs are known CPEB substrates, and none appear to be responsible for the effects on plasticity that are found in the CPEB knockout mouse. These results suggest that the translation of other mRNAs is regulated by CPEB. To identify them, we have developed a functional assay based on the polyadenylation of brain-derived mRNAs injected into Xenopus oocytes, a surrogate system that carries out this 3' end processing event in an efficient manner. The polyadenylated RNAs were isolated by binding to and thermal elution from poly(U) agarose and identified by microarray analysis. Selected sequences that were positive for polyadenylation were cloned and retested for polyadenylation by injection into oocytes. These sequences were then examined for activity-dependent polyadenylation in cultured hippocampal neurons. Finally, the levels of two proteins encoded by polyadenylated mRNAs were examined in glutamate-stimulated synaptoneurosomes. These studies show that many mRNAs undergo activity-dependent polyadenylation in neurons and that this process coincides with increased translation in the synapto-dendritic compartment.
DOI of Published Version
RNA. 2005 Sep;11(9):1340-7. Epub 2005 Jul 25. Link to article on publisher's site
RNA (New York, N.Y.)
Du, Ling and Richter, Joel D., "Activity-dependent polyadenylation in neurons" (2005). Open Access Articles. 1619.