biostudies-literatureUnknownLuo DNINDS NIH HHSNIH HHSSpinal muscular atrophy (SMA) genes, <i>SMN1</i> and <i>SMN2</i>, produce multiple circular RNAs (circRNAs), including C2A-2B-3-4 that encompasses early exons 2A, 2B, 3 and 4. Here we report the transcriptome- and proteome-wide effects of overexpression of C2A-2B-3-4 in inducible HEK293 cells. Our RNA-Seq analysis revealed altered expression of ~ 15% genes (4,172 genes) by C2A-2B-3-4. About half of the affected genes by C2A-2B-3-4 remained unaffected by L2A-2B-3-4, a linear transcript encompassing exons 2A, 2B, 3 and 4 of <i>SMN1/SMN2</i>. These fifindings underscore the unique role of the structural context of C2A-2B-3-4 in gene regulation. A surprisingly high number of upregulated genes by C2A-2B-3-4 were located on chromosomes 4 and 7, whereas many of the downregulated genes were located on chromosomes 10 and X. Supporting a cross-regulation of <i>SMN1/SMN2</i> transcripts, C2A-2B-3-4 and L2A-2B-3-4 upregulated and downregulated <i>SMN1/SMN2</i> mRNAs, respectively. Proteome analysis revealed 61 upregulated and 57 downregulated proteins by C2A-2B-3-4 with very limited overlap with those affected by L2A-2B-3-4. Independent validations confirmed the effect of C2A-2B-3-4 on expression of genes associated with chromatin remodeling, transcription, spliceosome function, ribosome biogenesis, lipid metabolism, cytoskeletal formation, cell proliferation and neuromuscular junction formation. Our findings reveal a broad role of C2A-2B-3-4, a universally expressed circRNA produced by <i>SMN1/SMN2</i>.Research squarers.3.rs-3818622https://www.ebi.ac.uk/biostudies/studies/S-EPMC10925445biostudies-literatureTranscriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.PMC10925445T35 OD027967R01 NS055925Singh ROttesen ELuo DLee JHfalseTranscriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.Spinal muscular atrophy (SMA) genes, <i>SMN1</i> and <i>SMN2</i>, produce multiple circular RNAs (circRNAs), including C2A-2B-3-4 that encompasses early exons 2A, 2B, 3 and 4. Here we report the transcriptome- and proteome-wide effects of overexpression of C2A-2B-3-4 in inducible HEK293 cells. Our RNA-Seq analysis revealed altered expression of ~ 15% genes (4,172 genes) by C2A-2B-3-4. About half of the affected genes by C2A-2B-3-4 remained unaffected by L2A-2B-3-4, a linear transcript encompassing exons 2A, 2B, 3 and 4 of <i>SMN1/SMN2</i>. These fifindings underscore the unique role of the structural context of C2A-2B-3-4 in gene regulation. A surprisingly high number of upregulated genes by C2A-2B-3-4 were located on chromosomes 4 and 7, whereas many of the downregulated genes were located on chromosomes 10 and X. Supporting a cross-regulation of <i>SMN1/SMN2</i> transcripts, C2A-2B-3-4 and L2A-2B-3-4 upregulated and downregulated <i>SMN1/SMN2</i> mRNAs, respectively. Proteome analysis revealed 61 upregulated and 57 downregulated proteins by C2A-2B-3-4 with very limited overlap with those affected by L2A-2B-3-4. Independent validations confirmed the effect of C2A-2B-3-4 on expression of genes associated with chromatin remodeling, transcription, spliceosome function, ribosome biogenesis, lipid metabolism, cytoskeletal formation, cell proliferation and neuromuscular junction formation. Our findings reveal a broad role of C2A-2B-3-4, a universally expressed circRNA produced by <i>SMN1/SMN2</i>.2024-01-01T00:00:00Z2024 Feb2025-04-04T19:15:26.155Z2025-04-04T19:15:26.155ZS-EPMC109254453846417410.21203/rs.3.rs-3818622/v1