XB-ART-47876Genome Res. January 1, 2014; 24 (1): 96-106.
Small RNA profiling of Xenopus embryos reveals novel miRNAs and a new class of small RNAs derived from intronic transposable elements.
Small RNA control of gene expression is critical for developmental processes in vertebrate embryos. To determine the dynamics of small RNA expression and to uncover novel small RNAs in the early vertebrate embryo, we performed high-throughput sequencing of all small RNAs in Xenopus tropicalis embryos at three developmental time points and in dissected halves of gastrula embryos. This analysis allowed us to identify novel microRNAs and we show that microRNA expression is highly dynamic and spatially localized in early embryos. In addition, we have developed a microRNA prediction pipeline and demonstrate that it has the power to predict new miRNAs that are experimentally detectable in frogs, mice, and humans. By combining the small RNA sequencing with mRNA profiling at the different developmental stages, we identify a new class of small noncoding RNAs that we name siteRNAs, which align in clusters to introns of protein-coding genes. We show that siteRNAs are derived from remnants of transposable elements present in the introns. We find that genes containing clusters of siteRNAs are transcriptionally repressed as compared with all genes. Furthermore, we show that this is true for individual genes containing siteRNA clusters, and that these genes are enriched in specific repressive histone modifications. Our data thus suggest a new mechanism of siteRNA-mediated gene silencing in vertebrates, and provide an example of how mobile elements can affect gene regulation.
PubMed ID: 24065776
PMC ID: PMC3875865
Article link: Genome Res.
Grant support: 1R01 DC011901-01 NIDCD NIH HHS , MC_U117560482 Medical Research Council , U117560482 Medical Research Council , Cancer Research UK, P40 OD010997 NIH HHS , 11832 Cancer Research UK, CRUK_11832 Cancer Research UK, R01 DC011901 NIDCD NIH HHS , MRC_MC_U117560482 Medical Research Council