Research Center in Infectious Diseases and Axis of Infectious and Immune Diseases, Research Center of the Centre Hospitalier Universitaire de Québec-Université Laval, QC, Quebec, Canada.
Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, University Laval, Quebec, QC, G1V 4G2, Canada.
BMC Biol. 2024 Oct 29;22(1):249. doi: 10.1186/s12915-024-02051-4.
The Leishmania genome harbors formerly active short interspersed degenerated retroposons (SIDERs) representing the largest family of repetitive elements among trypanosomatids. Their substantial expansion in Leishmania is a strong predictor of important biological functions. In this study, we combined multilevel bioinformatic predictions with high-throughput genomic and transcriptomic analyses to gain novel insights into the diversified roles retroposons of the SIDER2 subfamily play in Leishmania genome evolution and expression.
We show that SIDER2 retroposons form various evolutionary divergent clusters, each harboring homologous SIDER2 sequences usually located nearby in the linear sequence of chromosomes. This intriguing genomic organization underscores the importance of SIDER2 proximity in shaping chromosome dynamics and co-regulation. Accordingly, we show that transcripts belonging to the same SIDER2 cluster can display similar levels of expression. SIDER2 retroposons are mostly transcribed as part of 3'UTRs and account for 13% of the Leishmania transcriptome. Genome-wide expression profiling studies underscore SIDER2 association generally with low mRNA expression. The remarkable link of SIDER2 retroposons with downregulation of gene expression supports their co-option as major regulators of mRNA abundance. SIDER2 sequences also add to the diversification of the Leishmania gene expression repertoire since ~ 35% of SIDER2-containing transcripts can be differentially regulated throughout the parasite development, with a few encoding key virulence factors. In addition, we provide evidence for a functional bias of SIDER2-containing transcripts with protein kinase and transmembrane transporter activities being most represented.
Altogether, these findings provide important conceptual advances into evolutionary innovations of transcribed extinct retroposons acting as major RNA cis-regulators.
利什曼原虫基因组中存在以前活跃的短散在退化逆转录转座子（SIDER），它们是动基体目生物中最大的重复元件家族。它们在利什曼原虫中的大量扩张是重要生物学功能的强有力预测指标。在这项研究中，我们结合多层次生物信息学预测与高通量基因组和转录组分析，深入了解 SIDER2 亚家族逆转录转座子在利什曼原虫基因组进化和表达中的多样化作用。
我们表明，SIDER2 逆转录转座子形成各种进化上不同的簇，每个簇都含有同源的 SIDER2 序列，通常位于染色体线性序列的附近。这种引人入胜的基因组组织强调了 SIDER2 接近性在塑造染色体动态和共调控中的重要性。因此，我们表明属于同一 SIDER2 簇的转录本可以表现出相似的表达水平。SIDER2 逆转录转座子主要作为 3'UTR 的一部分转录，并占利什曼原虫转录组的 13%。全基因组表达谱研究强调 SIDER2 与低 mRNA 表达普遍相关。SIDER2 逆转录转座子与基因表达下调的显著关联支持了它们作为 mRNA 丰度主要调节因子的共同作用。SIDER2 序列还为利什曼原虫基因表达谱的多样化做出了贡献，因为约 35%的含有 SIDER2 的转录本可以在整个寄生虫发育过程中发生差异调节，其中一些编码关键的毒力因子。此外，我们提供了证据表明含有 SIDER2 的转录本具有功能偏向性，其中蛋白激酶和跨膜转运蛋白活性的转录本最为丰富。
总之，这些发现为作为主要 RNA 顺式调控因子的转录失活逆转录转座子的进化创新提供了重要的概念进展。
