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在小鼠垂体发育和成熟的激素分泌细胞中表达的长非编码 RNA。

Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells.

机构信息

Department of Human Genetics, University of Michigan, Ann Arbor, MI 41809-5618, USA.

Graduate Program in Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Endocrinology. 2024 Oct 30;165(12). doi: 10.1210/endocr/bqae147.

Abstract

Mammalian genomes contain thousands of genes for long noncoding RNA (lncRNAs), some of which have been shown to affect protein coding gene expression through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced, and polyadenylated, but not translated into protein. Nuclear lncRNAs can modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function. We mined transcriptome data from mouse pituitary glands collected at embryonic days 12.5 and 14.5 and identified over 200 different lncRNA transcripts. To develop a research resource for the study of lncRNA, we used pituitary cre transgenes to tag pituitary cell types in adult mice with fluorescent markers, and enriched for thyrotropes, gonadotropes, and somatotropes using fluorescence-activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNAs in adult pituitary cells; a few were located immediately nearby genes that encode pituitary hormones or lineage-specific transcription factors. The location of these lncRNAs suggests the possibility of a cis-acting regulatory role in pituitary development or function, and we observe coordinated expression of 2 of them with their putative target genes in transgenic mice. This research resource sets the foundation for examining the actions of lncRNAs on their putative target genes and determining whether they have roles during development and in response to physiological demand.

摘要

哺乳动物基因组包含数千个长非编码 RNA(lncRNA)基因,其中一些已被证明通过多种机制影响蛋白质编码基因的表达。lncRNA 转录本长度超过 200 个核苷酸,通常具有帽子结构、经过剪接和多聚腺苷酸化修饰,但不翻译成蛋白质。核内 lncRNA 可以通过与 DNA 相互作用、形成 R 环和募集调节蛋白,在转录水平上以顺式或反式方式修饰染色质结构和转录。关于 lncRNA 在垂体分化和功能中的作用,我们知之甚少。我们从收集自胚胎第 12.5 天和 14.5 天的小鼠垂体的转录组数据中挖掘出超过 200 种不同的 lncRNA 转录本。为了开发研究 lncRNA 的资源,我们使用垂体 cre 转基因在成年小鼠中用荧光标记标记垂体细胞类型,并使用荧光激活细胞分选富集促甲状腺素细胞、促性腺激素细胞和生长激素细胞。我们使用 RNA 测序确定每个细胞群体的转录组,并从数据中挖掘 lncRNA。我们在成年垂体细胞中检测到数百种 lncRNA,其中一些位于编码垂体激素或谱系特异性转录因子的基因附近。这些 lncRNA 的位置表明它们在垂体发育或功能中可能具有顺式作用的调节作用,我们在转基因小鼠中观察到其中 2 个与它们的假定靶基因协调表达。这个研究资源为研究 lncRNA 对其假定靶基因的作用以及确定它们在发育过程中和对生理需求的反应中是否具有作用奠定了基础。

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