The KLHL1-antisense transcript ( KLHL1AS) is evolutionarily conserved.
The KLHL1-antisense transcript ( KLHL1AS) is evolutionarily conserved.
复制标题
KLHL1 反义转录本 (KLHL1AS) 在进化上是保守的。
DOI：
10.1007/s00335-001-2105-2
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Koob,MichaelD
中科院分区：
文献类型：
--
作者：
Benzow,KellieA;Koob,MichaelD
脊髓小脑性共济失调8型（SCA 8）是由与Kelch样I（KLHLI）基因重叠的非翻译的内源性反义RNA中CTG扩增引起的。这种转录本的正常功能目前尚不清楚。我们现在已经鉴定了KLHL 1-反义（KLHLIAS）RNA的启动子区域，并报告了小鼠中也存在aKlhl 1 astransscript。人和小鼠Klhl 1AS的转录起始于KLHL 1第一内含子的同源启动子区，并延伸至转录和翻译起始位点以及KLHL 1的第一剪接供体序列。我们发现小鼠KlhlllasRNA不被剪接，终止于KlhlI启动子区的多聚腺苷酸化位点，而目前和以前的工作都表明，人类KLHLIAS高度剪接成含有多达6个外显子的加工转录本。从小脑和整个成人脑和整个胎儿组织中分离的RNA中检测到MouseKlhlIastranscript，睾丸和卵巢中的水平较低。类似地，人类KLHL 1AS在各种脑组织中表达，包括小脑，最受SCA 8影响的组织，并且在睾丸和肾脏中以低水平检测到。这种反义/正义转录组织的进化保守性强有力地表明，KLHLI AS转录本在人类和小鼠中都发挥着重要的生物学作用，可能是KLHLI表达的调节因子。
Spinocerebellar ataxia type 8 (SCA8) is caused by a CTG expansion in an untranslated, endogenous antisense RNA that overlaps theKelch-like I (KLHLI)gene. The normal function of this transcript is currently unknown. We have now identified the promoter region for theKLHL1-antisense (KLHLIAS)RNA and report that aKlhl1astranscript is present in the mouse as well. Human and mouseKlhl1ASare transcribed from homologous promoter regions in the first intron ofKLHLIand extend through the transcription and translation start sites as well as the first splice donor sequence ofKLHL1.We found that the mouseKlhlIasRNA is not spliced and terminates in a polyadenylation site in theKlhlIpromoter region, whereas both the present and previous work show that humanKLHLIASis highly variably spliced into processed transcripts that contain up to six exons. MouseKlhlIastranscript 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, humanKLHL1ASis 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 thatKLHLIAStranscripts play a significant biological role in both human and mouse, presumably as a regulator ofKLHLIexpression.