RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes. Although many editing sites have been identified in domestic pigs (Sus scrofa), little is known about the characteristics and dynamic regulation of RNA editing in the pineal gland (PG), a small neuroendocrine gland that synthesizes and secretes melatonin, which is primarily responsible to modulate sleep patterns. This study analyzed the expression of adenosine-to-inosine (A-to-I) editing regulators and profiled the first dynamic A-to-I RNA editome during postnatal PG development. The results identified ADAR1 as the most abundantly expressed ADAR enzyme, which was down-regulated during postnatal PG development. Furthermore, 47,284 high-confidence RNA editing sites were identified, the majority of which (93.6%) were of the canonical A-to-I editing type, followed by C-to-T editing. Analysis of its characteristics showed that the A-to-I editing sites mostly localized in SINE retrotransposons PRE-1/Pre0_SS. Moreover, a strong deficiency and preference for guanine nucleotides at positions of one base upstream or downstream were found, respectively. The overall editing level at the puberty stage was higher than at both infancy and adulthood stages. Additionally, genome-wide RNA editing was found to exhibit a dynamic stage-specific fashion (postnatally). Genes that underwent developmental changes in RNA editing were associated with catabolic processes as well as protein localization and transport functions, implying that RNA editing might be responsible for the molecular machineries of the postnatal developing PG. Remarkably, RNA editing in 3′-UTRs might regulate gene expression by influencing miRNA binding during PG development. This study profiles the first comprehensive developmental RNA editome in the pig PG, which contributes to the understanding of the importance of post-transcriptionally mediated regulation during mammalian postnatal PG development. Moreover, this study widely extends RNA editome resources in mammals.

中文翻译：

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猪出生后松果体发育阶段特异性 A-to-I 编辑模式 (Sus scrofa)。

RNA 编辑是哺乳动物基因组中广泛存在的转录后修饰机制。尽管在家猪 (Sus scrofa) 中发现了许多编辑位点，但对松果体 (PG) 中 RNA 编辑的特征和动态调控知之甚少，PG 是一种合成和分泌褪黑激素的小型神经内分泌腺，主要负责调节睡眠模式。本研究分析了腺苷转肌苷 (A-to-I) 编辑调节因子的表达，并分析了出生后 PG 发育过程中的第一个动态 A-to-I RNA 编辑组。结果确定 ADAR1 是表达最丰富的 ADAR 酶，在出生后 PG 发育过程中被下调。此外，还确定了 47,284 个高置信度 RNA 编辑位点，其中大部分（93.6%）属于典型的 A-to-I 编辑类型，然后是 C-to-T 编辑。对其特征的分析表明，A-to-I编辑位点主要定位于SINE反转录转座子PRE-1/Pre0_SS。此外，分别在上游或下游一个碱基的位置发现了对鸟嘌呤核苷酸的强烈缺乏和偏好。青春期的整体编辑水平高于婴儿期和成年期。此外，发现全基因组 RNA 编辑表现出动态的阶段特异性方式（出生后）。在 RNA 编辑中经历发育变化的基因与分解代谢过程以及蛋白质定位和转运功能相关，这意味着 RNA 编辑可能是产后发育 PG 的分子机制的原因。值得注意的是，3'-UTR 中的 RNA 编辑可能通过影响 PG 发育过程中的 miRNA 结合来调节基因表达。本研究描述了猪 PG 中第一个全面的发育 RNA 编辑组，这有助于理解哺乳动物出生后 PG 发育过程中转录后介导的调控的重要性。此外，这项研究广泛扩展了哺乳动物的 RNA 编辑组资源。