Reciprocal regulation of microRNA and mRNA profiles in neuronal development and synapse formation.
BACKGROUND
Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are now recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. While specific microRNAs are known to be involved in neural development, the extent to which global microRNA and mRNA profiles are coordinately regulated in neural development is unknown.


RESULTS
We examined mouse primary neuronal cultures, analyzing microRNA and mRNA expression. Three main developmental patterns of microRNA expression were observed: steady-state levels, up-regulated and down-regulated. Co-expressed microRNAs were found to have related target recognition sites and to be encoded in distinct genomic locations. A number of 43 differentially expressed miRNAs were located in five genomic clusters. Their predicted mRNA targets show reciprocal levels of expression. We identified a set of reciprocally expressed microRNAs that target mRNAs encoding postsynaptic density proteins and high-level steady-state microRNAs that target non-neuronal low-level expressed mRNAs.


CONCLUSIONS
We characterized hundreds of miRNAs in neuronal culture development and identified three major modes of miRNA expression. We predict these miRNAs to regulate reciprocally expressed protein coding genes, including many genes involved in synaptogenesis. The identification of miRNAs that target mRNAs during synaptogenesis indicates a new level of regulation of the synapse.
Manakov
Sergei A
SA
European Bioinformatics Institute, Hinxton, Cambridge CB101SD, UK.
Grant
Seth G N
SG
Enright
Anton J
AJ
D000818:Animals; D016000:Cluster Analysis; D004622:Embryo, Mammalian / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA
D035683:MicroRNAs; D012333:RNA, Messenger