title: The KLHL1-antisense transcript ( KLHL1AS) is evolutionarily conserved.
abstract: Spinocerebellar ataxia type 8 (SCA8) is caused by a CTG expansion in an untranslated, endogenous antisense RNA that overlaps the Kelch-like 1 ( KLHL1) gene. The normal function of this transcript is currently unknown. We have now identified the promoter region for the KLHL1-antisense ( KLHL1AS) RNA and report that a Klhl1as transcript is present in the mouse as well. Human and mouse KLHL1AS are transcribed from homologous promoter regions in the first intron of KLHL1 and extend through the transcription and translation start sites as well as the first splice donor sequence of KLHL1. We found that the mouse Klhl1as RNA is not spliced and terminates in a polyadenylation site in the Klhl1 promoter region, whereas both the present and previous work show that human KLHL1AS is highly variably spliced into processed transcripts that contain up to six exons. Mouse Klhl1as transcript was detected in RNA isolated from the cerebellum and from total adult brain and total fetal tissue, and at a low level in testis and ovary. Similarly, human KLHL1AS is expressed in various brain tissues, including the cerebellum, the tissue most affected by SCA8, and was detected at low levels in testis and kidney. The evolutionary conservation of this antisense/sense transcriptional organization strongly indicates that KLHL1AS transcripts play a significant biological role in both human and mouse, presumably as a regulator of KLHL1 expression.
authors.affiliation: Institute of Human Genetics, MMC 206 UMHC, 420 Delaware St. SE., University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Benzow
authors.forename: Michael D
authors.initials: MD
authors.lastname: Koob
mesh_terms: D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000737:chemistry; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics*; D017423:Sequence Analysis, RNA; D020754:Spinocerebellar Ataxias / Q000235:genetics
chemical_list: C412617:KLHL1 protein, human; D008840:Microfilament Proteins; D016372:RNA, Antisense