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在 HUSH 沉默的背景下,反转录副本的进化。

Evolution of retrocopies in the context of HUSH silencing.

机构信息

Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznańskiego 6, Poznań, Poland.

Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Garbary 15, Poznań, Poland.

出版信息

Biol Direct. 2024 Aug 2;19(1):60. doi: 10.1186/s13062-024-00507-9.

Abstract

Retrotransposition is one of the main factors responsible for gene duplication and thus genome evolution. However, the sequences that undergo this process are not only an excellent source of biological diversity, but in certain cases also pose a threat to the integrity of the DNA. One of the mechanisms that protects against the incorporation of mobile elements is the HUSH complex, which is responsible for silencing long, intronless, transcriptionally active transposed sequences that are rich in adenine on the sense strand. In this study, broad sets of human and porcine retrocopies were analysed with respect to the above factors, taking into account evolution of these molecules. Analysis of expression pattern, genomic structure, transcript length, and nucleotide substitution frequency showed the strong relationship between the expression level and exon length as well as the protective nature of introns. The results of the studies also showed that there is no direct correlation between the expression level and adenine content. However, protein-coding retrocopies, which have a lower adenine content, have a significantly higher expression level than the adenine-rich non-coding but expressed retrocopies. Therefore, although the mechanism of HUSH silencing may be an important part of the regulation of retrocopy expression, it is one component of a more complex molecular network that remains to be elucidated.

摘要

逆转录转座是导致基因重复进而引起基因组进化的主要因素之一。然而,经历这一过程的序列不仅是生物多样性的绝佳来源,在某些情况下,它们还会对 DNA 的完整性构成威胁。HUSH 复合物是防止移动元件掺入的机制之一,它负责沉默富含腺嘌呤的 sense 链上长的、无内含子、转录活跃的转座序列。在这项研究中,考虑到这些分子的进化,我们对人类和猪的大量 retrocopies 进行了上述因素的分析。对表达模式、基因组结构、转录本长度和核苷酸替换频率的分析表明,表达水平与外显子长度之间存在很强的相关性,内含子具有保护作用。研究结果还表明,表达水平与腺嘌呤含量之间没有直接的相关性。然而,腺嘌呤含量较低的编码蛋白的 retrocopies 的表达水平明显高于富含腺嘌呤但不表达的非编码 retrocopies。因此,尽管 HUSH 沉默机制可能是 retrocopy 表达调控的重要组成部分,但它是一个更复杂的分子网络的一个组成部分,有待进一步阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d18e/11295320/30e268a236c3/13062_2024_507_Fig1_HTML.jpg

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