Abstract
BackgroundRNA 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.ResultsThis 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.ConclusionsThis 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.
Highlights
RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes
To obtain the total amount of RNA editing in each pineal gland (PG) sample, we took all editing sites we identified into account and did not set any sequencing coverage criteria [9]
Expression of adenosine deaminase acting on the RNA (ADAR) during postnatal pineal gland development First, the temporal expression of ADAR enzymes in postnatal PG was evaluated by RNA-Seq
Summary
RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes. 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. RNA editing is a widespread post-transcription modification mechanism in mammalian genomes that alters the nucleotide composition at the RNA level, while no affecting the corresponding DNA sequence [1]. With regard to functional consequences, A-to-I editing at protein-coding regions can result in changes of amino acids [2]. A-to-I editing plays an important role in gene expression by modulating alternative splicing [3], editing miRNA sequences [4] and affecting miRNA binding sites [5]. A-to-I editing influences the propagation of fast electrical and chemical signals in nervous systems [6] and is both temporally and developmentally regulated during brain development and diseases [7, 8]
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