Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
Genetics, Hyogo College of Medicine, Hyogo, Japan.
Genes Cells. 2022 Jan;27(1):14-24. doi: 10.1111/gtc.12906. Epub 2021 Nov 30.
LincRNA-p21 is a long intergenic non-coding RNA (LincRNA) gene reported to activate the transcription of the adjacent Cdkn1a (p21) gene in cis. The importance of the enhancer elements in the LincRNA-p21 gene region has also been reported; however, the involvement of the LincRNA-p21 transcripts in regulating Cdkn1a in vivo is still unclear. In this study, we used a LincRNA-p21-trapped mouse line (LincRNA-p21 ) in which βgeo was inserted into intron 1, and all enhancer elements were retained. In LincRNA-p21 mice, the transcription of LincRNA-p21 was repressed due to the βgeo sequence, and the expression of exon 1 of LincRNA-p21 was restored through its deletion or replacement by another sequence, and Cdkn1a expression was also upregulated. Furthermore, regardless of the full-length transcripts, the expression of Cdkn1a correlated with the transcription of the exon 1 of LincRNA-p21. This result indicates that the LincRNA-p21 transcripts are not functional, but the transcriptional activity around exon 1 is important for Cdkn1a expression.
LincRNA-p21 是一种长链非编码 RNA（LincRNA）基因，据报道它可以在顺式激活邻近的 Cdkn1a（p21）基因的转录。LincRNA-p21 基因区域中增强子元件的重要性也已经被报道；然而，LincRNA-p21 转录本在体内调节 Cdkn1a 的参与仍然不清楚。在这项研究中，我们使用了一种 LincRNA-p21 捕获小鼠系（LincRNA-p21），其中βgeo 插入到内含子 1 中，并保留了所有的增强子元件。在 LincRNA-p21 小鼠中，由于 βgeo 序列，LincRNA-p21 的转录受到抑制，通过缺失或用另一个序列替换 LincRNA-p21 的外显子 1，恢复了 LincRNA-p21 的表达，同时也上调了 Cdkn1a 的表达。此外，无论全长转录本如何，Cdkn1a 的表达都与 LincRNA-p21 的外显子 1 的转录相关。这一结果表明，LincRNA-p21 转录本没有功能，但外显子 1 周围的转录活性对 Cdkn1a 的表达很重要。
