A natural antisense transcript against Rad18, specifically expressed in neurons and upregulated during beta-amyloid-induced apoptosis.
Apoptosis, the main form of programmed cell death, is associated to a complex and dynamic transcriptional and post-transcriptional programme. By microarray analysis, we have previously implicated 241 genes differentially expressed in rat cortical neurons exposed to beta-amyloid (Abeta) protein, the major constituent of amyloid plaques in Alzheimer's disease. A large number of identified genes have no name or known function. In the present study, we have investigated one of these genes that encodes for a natural antisense transcript against Rad18 (NAT-Rad18). Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) confirmed differential expression of this transcript in cortical neurons exposed to Abeta. In situ hybridization, qRT-PCR and immunohistochemistry were used to assess the regional and cellular distribution of NAT-Rad18 in adult rat brain. These experiments showed a widespread distribution of NAT-Rad18, with the highest levels in the cerebellum, brainstem and cortex, where it was specifically expressed by neurons. NAT-Rad18 was also strongly expressed in epithelial cells of choroid plexus and cerebral vessels. At the cellular level, expression of Rad18 was counterbalanced by that of its natural antisense transcript, as shown by both in situ hybridization and immunohistochemistry. These experiments suggest the existence of a NAT that exerts a post-transcriptional control over Rad18.
Parenti
Rosalba
R
Department of Physiological Sciences, University of Catania, 95125 Catania, Italy.
Paratore
Sabrina
S
Torrisi
Antonietta
A
Cavallaro
Sebastiano
S
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D016372:RNA, Antisense; C485953:Rad18 protein, mouse; C527167:Rad18 protein, rat