Identification of tRNA-derived small RNAs and their potential roles in porcine skeletal muscle with intrauterine growth restriction.

Identification of tRNA-derived small RNAs and their potential roles in porcine skeletal muscle with intrauterine growth restriction.
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tRNA 衍生的小 RNA 的鉴定及其在宫内生长受限的猪骨骼肌中的潜在作用

DOI:
10.3389/fphys.2022.962278
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发表时间:
2022
影响因子:
4
通讯作者:
--
中科院分区:
医学2区
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--
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胎儿宫内生长受限(IUGR)在人类中通常表现为生长不良和智力发育迟缓,而在家畜中它会导致死亡率增加。作为一种新的表观遗传调控分子,tRNA衍生的小RNAs(TsRNAs)已被报道参与多种生物学过程。本研究以35d龄猪为模型,通过对正常和IUGR猪骨骼肌中tsRNAs的测序,对tsRNAs进行了分析。共鉴定出586个tsRNAs,其中103个在正常体型猪中特异表达,38个在IUGR猪中特异表达。在成熟tRNA的5‘端反密码子(TRF-5c)之前剪接形成的tsRNAs占tsRNAs的90%以上,IUGR猪的tsRNAs显著高于正常体型猪。差异表达的tsRNAs靶基因的丰富途径主要包括代谢途径、Rap1信号途径、内吞作用、mTOR信号途径和AMPK信号途径。靶基因的调控网络分析表明,IGF1是IUGR和正常猪骨骼肌中最重要的调控节点分子之一。此外,IGF1还被发现是在IUGR猪中高表达的tsRNA TRF-Glu-TTC-047的靶基因之一。本文描述的发现揭示了tsRNAs在IUGR猪骨骼肌发育中的作用,从而为哺乳动物IUGR的预防和治疗提供了见解。
Intrauterine growth restriction (IUGR) in humans often manifests as poor growth and delayed intellectual development, whereas in domestic animals it results in increased mortality. As a novel epigenetic regulatory molecule, tRNA-derived small RNAs (tsRNAs) have been reported to be involved in many biological processes. In this study, pigs (35d) were used as a model to characterize tsRNAs by sequencing in normal and IUGR porcine skeletal muscle. A total of 586 tsRNAs were identified, of which 103 were specifically expressed in normal-size pigs and 38 were specifically expressed in IUGR pigs. The tsRNAs formed by splicing before the 5′ end anti codon of mature tRNA (tRF-5c) accounted for over 90% of tsRNAs, which were significantly enriched in IUGR pigs than in normal-size pigs. Enriched pathways of differentially expressed tsRNAs target genes mainly included metabolic pathways, Rap1 signaling pathway, endocytosis, mTOR signaling pathway, and AMPK signaling pathway. Regulatory network analysis of target genes revealed that IGF1 was one of the most important molecules of regulatory nodes in IUGR and normal porcine skeletal muscle. In addition, IGF1 was found to be one of the target genes of tRF-Glu-TTC-047, which is a highly expressed tsRNA in IUGR pigs. The findings described herein uncover the role of tsRNAs in IUGR porcine skeletal muscle development, thus providing insights into the prevention and treatment of IUGR in mammals.
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