PT - JOURNAL ARTICLE AU - Óscar García Blay AU - Pieter Verhagen AU - Benjamin Martin AU - Maike M.K. Hansen TI - RNA degradation heavily impacts mRNA co-expression AID - 10.1101/2022.09.21.508820 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.09.21.508820 4099 - http://biorxiv.org/content/early/2022/09/22/2022.09.21.508820.short 4100 - http://biorxiv.org/content/early/2022/09/22/2022.09.21.508820.full AB - Co-expression of genes measured with single-cell RNA sequencing is extensively utilized to understand the principles of gene regulation within and across cell types and species. It is assumed that the presence of correlation in gene expression values at the single-cell level demonstrates the existence of common regulatory mechanisms. However, the regulatory mechanisms that should lead to observed co-expression at an mRNA level often remain unexplored. Here we investigate the relationship between processes upstream and downstream of transcription (i.e., promoter architecture and coordination, DNA contact frequencies and mRNA degradation) and pairwise gene expression correlations at an mRNA level. We identify that differences in mRNA degradation (i.e., half-life) is a pivotal source of single-cell correlations in mRNA levels independently of the presence of common regulatory mechanisms. These findings reinforce the necessity of including post-transcriptional regulation mechanisms in the analysis of gene expression in mammalian cells.Competing Interest StatementThe authors have declared no competing interest.