A long non-coding RNA transcribed from conserved non-coding sequences contributes to the mouse prolyl oligopeptidase gene activation
A long non-coding RNA transcribed from conserved non-coding sequences contributes to the mouse prolyl oligopeptidase gene activation
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DOI：
10.1093/jb/mvt113
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发表时间：
2014-04-01
影响因子：
2.7
通讯作者：
Kimura, Atsushi P.
中科院分区：
文献类型：
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作者：
Matsubara, Shin;Kurihara, Misuzu;Kimura, Atsushi P.
脯氨酰寡肽酶(POP)是一种多功能的蛋白水解酶，参与多种生理活动，但其基因调控机制尚不清楚。为了鉴定新的POP基因调控元件，我们比较了小鼠和人类POP基因座的基因组序列，在相邻的基因间隔区发现了六个保守的非编码序列(CNS)。从这些CNS中转录出4个长非编码RNA(LncRNAs)，其中1个(LncPrep+96kb)的表达模式与POP的表达模式相关。由于转录起始点的不同，LncPrep+96kb被转录成两种形式，并定位于细胞核和细胞质，但在细胞核中存在更多。当我们在原代卵巢颗粒细胞和一种肝细胞系中敲除LncPrep+96kb后，两种细胞中POP的表达都降低了。相反，过表达LncPrep+96kb只增加颗粒细胞中POP的表达。由于LncPrep+96kb在激素处理的卵巢中上调的时间与POP的时间相同，因此该LncRNA可能在颗粒细胞POP基因的激活中发挥作用。此外，人类POP基因的下游区域也被转录。我们提出了一种新的POP基因激活机制。
Prolyl oligopeptidase (POP) is a multifunctional protease which is involved in many physiological events, but its gene regulatory mechanism is poorly understood. To identify novel regulatory elements of the POP gene, we compared the genomic sequences at the mouse and human POP loci and found six conserved non-coding sequences (CNSs) at adjacent intergenic regions. From these CNSs, four long non-coding RNAs (lncRNAs) were transcribed and the expression pattern of one (lncPrep+96kb) was correlated with that of POP. lncPrep+96kb was transcribed as two forms due to the different transcriptional start sites and was localized at the nucleus and cytoplasm, although more was present at the nucleus. When we knocked down lncPrep+96kb in the primary ovarian granulosa cell and a hepatic cell line, the POP expression was decreased in both cells. In contrast, overexpression of lncPrep+96kb increased the POP expression only in the granulosa cell. Because lncPrep+96kb was upregulated with the same timing as POP in the hormone-treated ovary, this lncRNA could play a role in the POP gene activation in the granulosa cell. Moreover, a downstream region of the human POP gene was also transcribed. We propose a novel mechanism for the POP gene activation.