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NMDtxDB: data-driven identification and annotation of human NMD target transcripts

The nonsense-mediated RNA decay (NMD) pathway is a crucial mechanism of mRNA quality control. Current annotations of NMD substrate RNAs are rarely data-driven, but use generally established rules. We present a data set with four cell lines and combinations for SMG5, SMG6, and SMG7 knockdowns or SMG7...

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Hauptverfasser: Britto-Borges, Thiago (VerfasserIn) , Gehring, Niels H. (VerfasserIn) , Böhm, Volker (VerfasserIn) , Dieterich, Christoph (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2024
In: RNA
Year: 2024, Jahrgang: 30, Heft: 10, Pages: 1277-1291
ISSN:1469-9001
DOI:10.1261/rna.080066.124
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1261/rna.080066.124
Verlag, kostenfrei, Volltext: https://rnajournal.cshlp.org/content/30/10/1277
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Verfasserangaben:Thiago Britto-Borges, Niels H. Gehring, Volker Boehm, and Christoph Dieterich

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520 |a The nonsense-mediated RNA decay (NMD) pathway is a crucial mechanism of mRNA quality control. Current annotations of NMD substrate RNAs are rarely data-driven, but use generally established rules. We present a data set with four cell lines and combinations for SMG5, SMG6, and SMG7 knockdowns or SMG7 knockout. Based on this data set, we implemented a workflow that combines Nanopore and Illumina sequencing to assemble a transcriptome, which is enriched for NMD target transcripts. Moreover, we use coding sequence information (CDS) from Ensembl, Gencode consensus Ribo-seq ORFs, and OpenProt to enhance the CDS annotation of novel transcript isoforms. In summary, 302,889 transcripts were obtained from the transcriptome assembly process, out of which 24% are absent from Ensembl database annotations, 48,213 contain a premature stop codon, and 6433 are significantly upregulated in three or more comparisons of NMD active versus deficient cell lines. We present an in-depth view of these results through the NMDtxDB database, which is available at https://shiny.dieterichlab.org/app/NMDtxDB, and supports the study of NMD-sensitive transcripts. We open sourced our implementation of the respective web-application and analysis workflow at https://github.com/dieterich-lab/NMDtxDB and https://github.com/dieterich-lab/nmd-wf. 
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