Comprehensive analysis of nonsense-mediated mRNA decay targets and activity in cardiomyocytes
Naghizadeh, M.; Alameldeen, A.; Kistler, R.; Lindner, D.; Kamuf-Schenk, V.; Volkers, M.; Schott, J.; Seeger, T.; Stoecklin, G.
Show abstract
Nonsense-mediated mRNA decay (NMD) serves as a mechanism to suppress the expression of mutant alleles containing premature termination codons, limit the expression of aberrantly spliced transcript isoforms, and control the expression of numerous regular genes. While the principles by which NMD recognizes target transcripts are well understood, much less is known about the range of mRNAs subject to NMD in tissues and specialized cell types. Here we describe the landscape of genes whose expression is controlled by NMD in cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM), using small read RNA sequencing in combination with a potent inhibitor of SMG1, a kinase essential for NMD. We find that NMD targets are highly conserved between iPSC-CM lines derived from two healthy individuals. Beyond gene level analysis, we identify individual exon and intron RNA sequences that strongly accumulate upon SMG1 inhibition. Using the cardiac NMD targets identified at gene, exon and intron level, we then demonstrate reduced NMD efficiency upon knockdown of two essential NMD factors, UPF1 and UPF2, in iPSC-CM. Our analysis demonstrates that quantifying the transcriptome-wide response to SMG1 inhibition represents a highly sensitive approach to assess global activity of the NMD pathway.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells 94%
- LDB1 regulates gene expression and chromatin structure in pluripotency and lineage differentiation 93%
- Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase 92%
Similar papers in this journal
- RAB18 is a key regulator of GalNAc conjugated siRNA induced silencing in Hep3B cells 92%
- Allele-specific CRISPR/Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy 91%
- Multiplex HDR for Disease and Correction Modeling of SCID by CRISPR Genome Editing in Human HSPCs 91%
Similar papers in this journal
- Human iPSC-Based Model Reveals NOX4 as Therapeutic Target in Duchenne Cardiomyopathy 95%
- iPSC culture expansion selects against putatively actionable mutations in the mitochondrial genome 95%
- Canonical Wnt pathway controls mESCs self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions 94%
Similar papers in this journal
Similar papers in this journal
- A Genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma 94%
- Modeling and Correction of Protein Conformational Disease in iPSC-derived Neurons through Personalized Base Editing 94%
- RNA splicing variants of the novel long non-coding RNA, CyKILR, possess divergent biological functions in non-small cell lung cancer 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.