Comparative analysis of multiple human cell lines reveals distinct stability regulation of alternative polyadenylation isoforms and mitochondrial RNAs in neuronal cells

ABSTRACT: mRNA stability plays an important role in gene expression. Here, using 3’ end sequencing of newly made and steady-state poly(A)+ RNAs, we compare transcript stability in multiple human cell lines, including HEK293T, HepG2, SH-SY5Y. We show that while mRNA stability is generally conserved across the cell lines, specific transcripts having high GC content and likely more stable secondary RNA structures are relatively more stable in SH-SY5Y cells compared to other two. These features also differentiate alternative polyadenylation (APA) 3’UTR isoforms in their stability difference in a cell type-specific manner. By analyzing cell differentiation of a neural stem cell line, we show that mRNA stability difference could contribute to gene expression changes in neurogenesis and confirms the neuronal identity of SH-SY5Y cells at gene expression and APA levels. Through comparison of APA isoforms, we show that mRNA stability control buffer the cleavage and polyadenylation site (PAS) choice in the cells studied. In addition, transcripts using intronic PAS are generally less stable, especially when the intron harboring the PAS is large and has a strong 5’ splice site, suggesting that intronic polyadenylation mostly plays a negative role in gene expression. Moreover, we found that poly(A)+ RNAs encoded by the mitochondrial genome are more stable in SH-SY5Y cells than the other two cell types, suggesting that mitochondrial RNA metabolism is distinct in neurons. Together, our results reveal multiple cell-specific mechanisms by which mRNA stability could contribute to the gene expression and APA programs that are important for cell identity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189899 | GEO | 2021/12/27

REPOSITORIES: GEO