Dataset Information

Modeling of Genome-Wide Polyadenylation Signals in Xenopus tropicalis.

ABSTRACT: Alternative polyadenylation (APA) is an important post-transcriptional modification event to process messenger RNA (mRNA) for transcriptional termination, transport, and translation. In the present study, we characterized poly(A) signals in Xenopus tropicalis using 70,918 highly confident poly(A) sites derived from 16,511 protein-coding genes to understand their roles in the regulation of embryo development and gender difference. We examined potential factors, including the gene length, the number of introns in a gene, and the intron length, that may affect the prevalence of APA. We observed 12 prominent poly(A) signal patterns, which accounted for approximately 92% of total APA sites in Xenopus tropicalis. Among them, three patterns are specific to X. tropicalis, so they are absent in other animals such as humans or mice. We catalogued APA sites based on their genomic regions and developed a bioinformatics pipeline to identify over-represented signal patterns for each class. Then the schema of cis elements for APA sites in each genomic region was proposed. More importantly, APA usage is dramatically dynamic in embryos along five developmental stages and well-coordinated with the maternal-to-zygotic transition event. We used an entropy-based method to identify developmental stage-specific APA sites and identified significant signal patterns around specific sites and constitutive sites. We found that the APA frequency in different genomic regions varies with developmental stages and that those sites located in intron or coding sequence regions contribute most to the dynamics of gene expression during developmental stages. This study deciphers the characteristics and poly(A) signal patterns for both canonical APA sites and non-canonical APA sites across different developmental stages and gender dimorphisms in X. tropicalis, providing new insights into the dynamic regulation of distal and proximal APA.

SUBMITTER: Zhu S

PROVIDER: S-EPMC6616101 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Modeling of Genome-Wide Polyadenylation Signals in <i>Xenopus tropicalis</i>.

Zhu Sheng S Wu Xiaohui X Fu Hongjuan H Ye Congting C Chen Moliang M Jiang Zhihua Z Ji Guoli G

Frontiers in genetics 20190703

Alternative polyadenylation (APA) is an important post-transcriptional modification event to process messenger RNA (mRNA) for transcriptional termination, transport, and translation. In the present study, we characterized poly(A) signals in <i>Xenopus tropicalis</i> using 70,918 highly confident poly(A) sites derived from 16,511 protein-coding genes to understand their roles in the regulation of embryo development and gender difference. We examined potential factors, including the gene length, t ...[more]

PMID: 31333724

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Project description:Emerging infectious diseases are of great concern for both wildlife and humans. Several highly virulent fungal pathogens have recently been discovered in natural populations, highlighting the need for a better understanding of fungal-vertebrate host-pathogen interactions. Because most fungal pathogens are not fatal in the absence of other predisposing conditions, host-pathogen dynamics for deadly fungal pathogens are of particular interest. The chytrid fungus Batrachochytrium dendrobatidis (hereafter Bd) infects hundreds of species of frogs in the wild. It is found worldwide and is a significant contributor to the current global amphibian decline. However, the mechanism by which Bd causes death in amphibians, and the response of the host to Bd infection, remain largely unknown. Here we use whole-genome microarrays to monitor the transcriptional responses to Bd infection in the model frog species, Silurana (Xenopus) tropicalis, which is susceptible to chytridiomycosis. To elucidate the immune response to Bd and evaluate the physiological effects of chytridiomycosis, we measured gene expression changes in several tissues (liver, skin, spleen) following exposure to Bd. We detected a strong transcriptional response for genes involved in physiological processes that can help explain some clinical symptoms of chytridiomycosis at the organismal level. However, we detected surprisingly little evidence of an immune response to Bd exposure, suggesting that this susceptible species may not be mounting efficient innate and adaptive immune responses against Bd. The weak immune response may be partially explained by the thermal conditions of the experiment, which were optimal for Bd growth. However, many immune genes exhibited decreased expression in Bd-exposed frogs compared to control frogs, suggesting a more complex effect of Bd on the immune system than simple temperature-mediated immune suppression. This study generates important baseline data for ongoing efforts to understand differences in response to Bd between susceptible and resistant frog species and the effects of chytridiomycosis in natural populations.

Project description:MotivationPre-mRNA cleavage and polyadenylation are essential steps for 3'-end maturation and subsequent stability and degradation of mRNAs. This process is highly controlled by cis-regulatory elements surrounding the cleavage/polyadenylation sites (polyA sites), which are frequently constrained by sequence content and position. More than 50% of human transcripts have multiple functional polyA sites, and the specific use of alternative polyA sites (APA) results in isoforms with variable 3'-untranslated regions, thus potentially affecting gene regulation. Elucidating the regulatory mechanisms underlying differential polyA preferences in multiple cell types has been hindered both by the lack of suitable data on the precise location of cleavage sites, as well as of appropriate tests for determining APAs with significant differences across multiple libraries.ResultsWe applied a tailored paired-end RNA-seq protocol to specifically probe the position of polyA sites in three human adult tissue types. We specified a linear-effects regression model to identify tissue-specific biases indicating regulated APA; the significance of differences between tissue types was assessed by an appropriately designed permutation test. This combination allowed to identify highly specific subsets of APA events in the individual tissue types. Predictive models successfully classified constitutive polyA sites from a biologically relevant background (auROC = 99.6%), as well as tissue-specific regulated sets from each other. We found that the main cis-regulatory elements described for polyadenylation are a strong, and highly informative, hallmark for constitutive sites only. Tissue-specific regulated sites were found to contain other regulatory motifs, with the canonical polyadenylation signal being nearly absent at brain-specific polyA sites. Together, our results contribute to the understanding of the diversity of post-transcriptional gene regulation.AvailabilityRaw data are deposited on SRA, accession numbers: brain SRX208132, kidney SRX208087 and liver SRX208134. Processed datasets as well as model code are published on our website: http://www.genome.duke.edu/labs/ohler/research/UTR/.Contactuwe.ohler@duke.edu.

Dataset Information

Modeling of Genome-Wide Polyadenylation Signals in Xenopus tropicalis.

Publications

Modeling of Genome-Wide Polyadenylation Signals in <i>Xenopus tropicalis</i>.

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