Spatiotemporal regulation of multiple overlapping sense and novel natural antisense transcripts at the Nrgn and Camk2n1 gene loci during mouse cerebral corticogenesis.
Nrgn and Camk2n1 are highly expressed in the brain and play an important role in synaptic long-term potentiation via regulation of Ca(2+)/calmodulin-dependent protein kinase II. We have shown that the gene loci for these 2 proteins are actively transcribed in the adult cerebral cortex and feature multiple overlapping transcripts in both the sense and antisense orientations with alternative polyadenylation. These transcripts were upregulated in the adult compared with embryonic and P1.5 mouse cerebral cortices, and transcripts with different 3' untranslated region lengths showed differing expression profiles. In situ hybridization (ISH) analysis revealed spatiotemporal regulation of the Nrgn and Camk2n1 sense and natural antisense transcripts (NATs) throughout cerebral corticogenesis. In addition, we also demonstrated that the expression of these transcripts was organ-specific. Both Nrgn and Camk2n1 sense and NATs were also upregulated in differentiating P19 teratocarcinoma cells. RNA fluorescent ISH analysis confirmed the capability of these NATs to form double-stranded RNA aggregates with the sense transcripts in the cytoplasm of cells obtained from the brain. We propose that the differential regulation of multiple sense and novel overlapping NATs at the Nrgn and Camk2n1 loci will increase the diversity of posttranscriptional regulation, resulting in cell- and time-specific regulation of their gene products during cerebral corticogenesis and function.
Ling
King-Hwa
KH
Department of Molecular Pathology, The Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia.
Hewitt
Chelsee A
CA
Beissbarth
Tim
T
Hyde
Lavinia
L
Cheah
Pike-See
PS
Smyth
Gordon K
GK
Tan
Seong-Seng
SS
Hahn
Christopher N
CN
Thomas
Tim
T
Thomas
Paul Q
PQ
Scott
Hamish S
HS
D000818:Animals; D015139:Blotting, Southern; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000254:growth & development* / Q000502:physiology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics*; D051579:Neurogranin / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
C496650:Nrgn protein, mouse; D016372:RNA, Antisense; D012333:RNA, Messenger; D051579:Neurogranin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2