逆转录mirs:源于mRNA逆转录转位的新型功能性mirna。

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Mobile DNA Pub Date : 2023-09-08 DOI:10.1186/s13100-023-00301-w
Rafael L V Mercuri, Helena B Conceição, Gabriela D A Guardia, Gabriel Goldstein, Maria D Vibranovski, Ludwig C Hinske, Pedro A F Galante
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引用次数: 0

摘要

背景:基因逆转录拷贝(retrocopies)已成为进化新颖性的主要来源。MicroRNAs (miRNAs)是一种小而高度保守的RNA分子,是基因表达的关键转录后调节因子。mirna的起源和随后的进化已经被解决,但尚未完全阐明。结果:在这项研究中,我们通过逆转录mRNA序列(retro-miRs)对miRNA的起源进行了全面的研究。我们从mRNA逆转录拷贝中鉴定出17个逆转录mirs。这些逆转录mirna中有4个在逆转录序列中从头开始,而13个逆转录mirna位于外显子区域,并与其宿主mrna一起复制。我们发现逆转录mirs具有灵长类特异性,包括5个在所有灵长类动物中保守的逆转录mirs和2个人类特异性的逆转录mirs。除miR-10527外,所有逆转录mirs均表达了预测和实验验证的靶基因。值得注意的是,逆转录mirs的靶基因参与了关键的生物学过程,如代谢过程、细胞信号传导和中枢神经系统神经递质的调节。此外,我们发现这些逆转录mirs通过靶向关键的癌症基因在癌症中发挥潜在的致癌作用,并在几种癌症类型中过度表达,包括肝细胞癌和胃腺癌。结论:我们的研究结果表明,mRNA逆转录转位是灵长类动物产生新型mirna(逆转录- mirs)的关键机制。这些逆转录mirs是表达的,保守的,具有重要细胞功能的靶基因,在癌症中发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Retro-miRs: novel and functional miRNAs originating from mRNA retrotransposition.

Background: Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated.

Results: In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma.

Conclusions: Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer.

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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
期刊最新文献
International congress on transposable elements (ICTE 2024) in Saint Malo: breaking down transposon waves and their impact. Accelerating de novo SINE annotation in plant and animal genomes. Association of hyperactivated transposon expression with exacerbated immune activation in systemic lupus erythematosus. Widespread HCD-tRNA derived SINEs in bivalves rely on multiple LINE partners and accumulate in genic regions. Correction: Transposon-derived introns as an element shaping the structure of eukaryotic genomes.
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