IGHMBP2 deletion suppresses translation and activates the integrated stress response [Ribo-Seq]

IGHMBP2 is a non-essential, superfamily 1 DNA/RNA helicase with incompletely understood biological function. Mutagenesis in IGHMBP2 is found in patients with rare neuromuscular diseases SMARD1 and CMT2S. IGHMBP2 is implicated in translational and transcriptional regulation via biochemical association with ribosomal proteins, pre-rRNA processing factors, and tRNA-related species. To uncover the cellular consequences of perturbing IGHMBP2, we generated full and partial IGHMBP2 deletion K562 cell lines. We performed Ribo-seq and RNA-seq and identified diverse gene expression changes due to IGHMBP2 deletion, including ATF4 upregulation. Overall design: We performed Ribo-seq and RNA-seq using two replicates per samples including K562 CRISPRi parental cells and K562 CRISPRi monoclonal cell lines with partial "HET" (two separate clones) versus full deletion "KO" (two separate clones) of IGHMBP2. We performed differential expression analysis among "HET" and "KO" genotypes relative to parental cell lines as the control.