Complex Analysis of Retroposed Genes' Contribution to Human Genome, Proteome and Transcriptome
Complex Analysis of Retroposed Genes' Contribution to Human Genome, Proteome and Transcriptome
复制标题
DOI：
10.3390/genes11050542
复制
发表时间：
2020-05-01
期刊：
影响因子：
3.5
通讯作者：
Makalowska, Izabela
中科院分区：
文献类型：
--
作者：
Kubiak, Magdalena Regina;Szczesniak, Michal Wojciech;Makalowska, Izabela
基因复制是生物进化的主要驱动力。基因复制的主要机制之一是逆转录，即mRNA首先转录成DNA，然后重新整合到基因组中的过程。大多数基因逆转录都缺乏调控区。然而，功能性逆转录基因的例子正在迅速增加。这些功能来自新的时空表达模式的获得，由插入的cDNA周围的基因组序列的内容和/或由选择性有利的突变施加，这可能导致从蛋白质编码到调节RNA的切换。最近的研究表明，这些基因可能通过与其他基因、新的调控RNA或其他调控元件融合而导致新的蛋白质结构域形成。我们利用高通量技术的现有数据来创建对retrogenes功能的复杂描述。我们的分析导致了人类逆转录基因的识别，大大有助于转录组和蛋白质组。这些逆转录拷贝证明了编码蛋白质或短肽的潜力，充当顺式和反式天然反义转录物（NATs），通过竞争相同的微小RNA来调节其祖细胞的表达，并为lncRNA提供序列和现有蛋白质的新外显子编码基因。我们的研究还表明，反转录，类似于反转录转座子，可以作为重组热点。据我们所知，这是第一个复杂的分析，这些功能的追溯。
Gene duplication is a major driver of organismal evolution. One of the main mechanisms of gene duplications is retroposition, a process in which mRNA is first transcribed into DNA and then reintegrated into the genome. Most gene retrocopies are depleted of the regulatory regions. Nevertheless, examples of functional retrogenes are rapidly increasing. These functions come from the gain of new spatio-temporal expression patterns, imposed by the content of the genomic sequence surrounding inserted cDNA and/or by selectively advantageous mutations, which may lead to the switch from protein coding to regulatory RNA. As recent studies have shown, these genes may lead to new protein domain formation through fusion with other genes, new regulatory RNAs or other regulatory elements. We utilized existing data from high-throughput technologies to create a complex description of retrogenes functionality. Our analysis led to the identification of human retroposed genes that substantially contributed to transcriptome and proteome. These retrocopies demonstrated the potential to encode proteins or short peptides, act as cis- and trans- Natural Antisense Transcripts (NATs), regulate their progenitors' expression by competing for the same microRNAs, and provide a sequence to lncRNA and novel exons to existing protein-coding genes. Our study also revealed that retrocopies, similarly to retrotransposons, may act as recombination hot spots. To our best knowledge this is the first complex analysis of these functions of retrocopies.