Heterogeneity in mRNA Translation

During mRNA translation, the genetic information stored in mRNA is translated into a protein sequence. It is imperative that the genetic information is translated with high precision. Surprisingly, however, recent experimental evidence has demonstrated that translation can be highly heterogeneous, even among different mRNA molecules derived from a single gene in an individual cell; multiple different polypeptides can be produced from a single mRNA molecule and the rate of translation can vary in both space and time. However, whether translational heterogeneity serves an important cellular function, or rather predominantly represents gene expression ‘noise’ remains an open question. In this review, we discuss the molecular basis and potential functions of such translational heterogeneity. Different types of translational heterogeneity can be distinguished: cell or tissue heterogeneity (translation of a gene differs in distinct cell or tissue types), ‘intergenic’ heterogeneity (mRNAs derived from different genes are translated differentially), and ‘intragenic’ heterogeneity (different mRNAs derived from one gene in a single cell show translational heterogeneity).Recent studies using single-molecule imaging have revealed the widespread occurrence of intragenic translational heterogeneity.Intragenic translational heterogeneity can have multiple origins, including heterogeneity in primary mRNA sequence, RNA-binding proteins, RNA modifications, mRNA structure, and ribosome composition.Translational heterogeneity is likely to represent ‘noise’ as well as spatiotemporal regulation of translation.