Cerebral ischemia induces neuronal expression of novel VL30 mouse retrotransposons bound to polyribosomes.
Mammalian genomes are burdened with a large heterogeneous group of endogenous replication defective retroviruses (retrotransposons). Previously, we identified a transcript resembling a virus-like 30S (VL30) retrotransposon increasing in mouse brain following transient cerebral ischemia. Paradoxically, this non-coding RNA was found bound to polyribosomes. Further analysis revealed that multiple retrotransposon species (BVL-1-like and mVL30-1-like) were bound to polyribosomes and induced by ischemia. These VL30 transcripts remained associated with polyribosomes in the presence of 0.5 M KCl, indicating that VL30 mRNA was tightly associated with ribosomal subunits. Furthermore, the profile of BVL-1 distribution on polyribosomal profiles was distinct from those of translated and translationally repressed mRNA. Consistent with expectations, 5.0 kb VL30 transcripts were detected in ischemic brain with a temporal pattern of expression that was distinct from c-fos. Expression of VL30 was localized in neurons using a combination of in situ hybridization and immunocytochemistry. 3'-RACE-PCR experiments yielded two unique sequences (VL30x-1 and VL30x-2) that were homologous to known VL30 genes. Phylogenetic analysis of VL30 promoter sequence (U3 region) resulted in the identification of two large VL30 subgroups. VL30x-1 and VL30x-2 were closely related and classified in a group that was distinct from the well-characterized VL30 genes BVL-1 and mVL30-1. The promoter regions of VL30x-1 and VL30x-2 did not possess the consensus sequences for either hypoxia or anoxia response elements, suggesting an alternative mechanism for induction. This is the first report that demonstrates ischemia-induced, neuronal expression of unique VL30 retrotransposons in mouse brain.
Costain
Willard J
WJ
Institute for Biological Sciences M54, National Research Council, Montreal Road Laboratories, Ottawa, ON, Canada K1A 0R6. Will.Costain@nrc-cnrc.gc.ca
Rasquinha
Ingrid
I
Graber
Tyson
T
Luebbert
Christian
C
Preston
Edward
E
Slinn
Jacqueline
J
Xie
Xiaoqi
X
MacManus
John P
JP
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002544:Cerebral Infarction / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D011132:Polyribosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018626:Retroelements / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D018626:Retroelements