Ramani, A. K., Nelson, A. C., Kapranov, P., Bell, I., Gingeras, T. R., Fraser, A. G. (2009) High resolution transcriptome maps for wild-type and nonsense-mediated decay-defective Caenorhabditis elegans. Genome Biology, 10 (9). R101. ISSN 1465-6906
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Abstract
BACKGROUND: While many genome sequences are complete, transcriptomes are less well characterized. We used both genome-scale tiling arrays and massively parallel sequencing to map the Caenorhabditis elegans transcriptome across development. We utilized this framework to identify transcriptome changes in animals lacking the nonsense-mediated decay (NMD) pathway. RESULTS: We find that while the majority of detectable transcripts map to known gene structures, >5% of transcribed regions fall outside current gene annotations. We show that >40% of these are novel exons. Using both technologies to assess isoform complexity, we estimate that >17% of genes change isoform across development. Next we examined how the transcriptome is perturbed in animals lacking NMD. NMD prevents expression of truncated proteins by degrading transcripts containing premature termination codons. We find that approximately 20% of genes produce transcripts that appear to be NMD targets. While most of these arise from splicing errors, NMD targets are enriched for transcripts containing open reading frames upstream of the predicted translational start (uORFs). We identify a relationship between the Kozak consensus surrounding the true start codon and the degree to which uORF-containing transcripts are targeted by NMD and speculate that translational efficiency may be coupled to transcript turnover via the NMD pathway for some transcripts. CONCLUSIONS: We generated a high-resolution transcriptome map for C. elegans and used it to identify endogenous targets of NMD. We find that these transcripts arise principally through splicing errors, strengthening the prevailing view that splicing and NMD are highly interlinked processes.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Algorithms Alternative Splicing Animals Caenorhabditis elegans/*genetics Codon, Nonsense/*genetics Gene Expression Profiling/*methods Genome, Helminth/genetics Genomics/methods Mutation Oligonucleotide Array Sequence Analysis/methods RNA Splice Sites/genetics RNA, Messenger/genetics/metabolism Sequence Analysis, DNA/methods Signal Transduction/genetics Transcription, Genetic/*genetics |
| Subjects: | organism description > animal > C elegans bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes |
| CSHL Authors: | |
| Communities: | CSHL labs > Gingeras lab |
| Depositing User: | Matt Covey |
| Date: | 2009 |
| Date Deposited: | 21 Mar 2014 19:34 |
| Last Modified: | 21 Mar 2014 19:34 |
| PMCID: | PMC2768976 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/29696 |
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