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Caenorhabditis japonica high resolution developmental transcriptomic time-course

ABSTRACT: Transcriptomic studies typically examine expression at the gene level, although it has been long recognized that the same genetic locus may produce isoforms distinct in their splicing and site of polyadenylation. Here we examine alternatively polyadenylated (APA) transcripts throughout embryogenesis and discover distinct strategies for gene regulation. We introduce APA-Seq, an RNA-Seq method to study APA at a global level, and apply it to study individual C. elegans embryos throughout early development. Surprisingly, we find that genes, whose overall expression is constitutive throughout development, generally show highly dynamic expression for individual isoforms. Such genes tend to participate in cellular as opposed to developmental processes, and this trend was also evident in the closely related C. japonica nematode, providing evidence that the manner by which cellular processes are regulated during embryogenesis is evolutionarily conserved. Finally, we report that genes with dynamic isoform usage have significantly more miRNA binding sites relative to constitutively-expressed isoforms, suggesting strong miRNA regulation in the control of isoform expression. Our findings support a model distinguishing two modes of gene regulatory underlying embryonic development each with unique functions and mechanisms.

ORGANISM(S): Caenorhabditis japonica

PROVIDER: GSE102398 | GEO | 2018/07/31

REPOSITORIES: GEO

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m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveal the census and complexity of the m6A epitranscriptome

Project description:N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (âm6A levelsâ), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3â untranslated regions (3â-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates

2016-06-24 | E-GEOD-66086 | biostudies-arrayexpress

m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveal the census and complexity of the m6A epitranscriptome

Project description:N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (“m6A levels”), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3’ untranslated regions (3’-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications.

2016-06-24 | GSE66086 | GEO

Alternative cleavage and polyadenylation analysis in an isoform-resolved way by Second- and Third-Generation Sequencing technologies

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Alternative Isoform Regulation in Human Tissue Transcriptomes

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2008-09-30 | E-GEOD-12946 | biostudies-arrayexpress

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2019-06-01 | GSE102357 | GEO

Alternative 3’UTRs play a widespread role in translation-independent mRNA association with endoplasmic reticulum

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2022-12-28 | GSE86179 | GEO

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2021-11-26 | GSE165742 | GEO

Alternative Isoform Regulation in Human Tissue Transcriptomes

2008-10-01 | GSE12946 | GEO

Analysis of alternative cleavage and polyadenylation by 3' region extraction and deep sequencing

Project description:Alternative cleavage and polyadenylation (APA) generates diverse mRNA isoforms. We developed 3' region extraction and deep sequencing (3'READS) to address mispriming issues that commonly plague poly(A) site (pA) identification, and we used the method to comprehensively map pAs in the mouse genome. Thorough annotation of gene 3' ends revealed over 5,000 previously overlooked pAs (~8% of total) flanked by A-rich sequences, underscoring the necessity of using an accurate tool for pA mapping. About 79% of mRNA genes and 66% of long noncoding RNA genes undergo APA, but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Quantitative analysis of APA isoforms by 3'READS indicated that promoter-distal pAs, regardless of intron or exon locations, become more abundant during embryonic development and cell differentiation and that upregulated isoforms have stronger pAs, suggesting global modulation of the 3' endM-bM-^@M-^Sprocessing activity in development and differentiation. 3'READS to map pAs in mouse genome

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