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Related Articles High resolution transcriptome maps for wild-type and NMD mutant C. elegans through development.
Genome Biol. 2009 Sep 24;10(9):R101
Authors: Ramani AK, Nelson AC, Kapranov P, Bell I, Gingeras TR, Fraser AG
ABSTRACT: BACKGROUND: While many genome sequences are complete, transcriptomes are less well characterised. We used both genome-scale tiling arrays and massively parallel sequencing to map the C. 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 nonsense-mediated decay (NMD). NMD prevents expression of truncated proteins by degrading transcripts containing premature termination codons (PTCs). We find that ~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.
PMID: 19778439 [PubMed - as supplied by publisher]
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Related Articles High resolution transcriptome maps for wild-type and NMD mutant C. elegans through development.
Genome Biol. 2009 Sep 24;10(9):R101
Authors: Ramani AK, Nelson AC, Kapranov P, Bell I, Gingeras TR, Fraser AG
ABSTRACT: BACKGROUND: While many genome sequences are complete, transcriptomes are less well characterised. We used both genome-scale tiling arrays and massively parallel sequencing to map the C. 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 nonsense-mediated decay (NMD). NMD prevents expression of truncated proteins by degrading transcripts containing premature termination codons (PTCs). We find that ~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.
PMID: 19778439 [PubMed - as supplied by publisher]
More...