Don't go in circles: confounding factors in gene expression profiling

Quantification of gene expression is a crucial research tool in the life sciences, which makes it important to identify any factors that could compromise its accuracy. One of these factors are non‐polyadenylated (poly(A) − ) transcripts, including circular RNAs (circRNAs) that can skew quantification of gene expression as they resemble messenger RNAs (mRNAs). Here, we highlight the impact circRNAs and other poly(A) − transcripts have on gene expression profiling and the biological conclusions drawn from such experiments. We also propose easily adoptable strategies to increase the accuracy of gene expression quantification. Graphical Abstract Circular RNAs arise from back‐splicing of linear pre‐mRNAs and therefore lack a poly(A) tail. While the discovery of these RNAs has triggered new questions in biology, they also illustrate an important caveat in widely used techniques for mRNA quantification.