Cis-regulatory RNA elements that regulate specialized ribosome activity

Abstract

Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

Keywords: 5′UTR; IRES; RNA element; specialized ribosome; translation; translational inhibitory element.

Figure 1.

A Translation Inhibitory Element (TIE) in the 5′UTRs of certain mRNAs inhibits cap-dependent translation and frees the mRNA from cap-dependent translational regulation. An additional cis-regulatory element, the Internal Ribosome Entry Site (IRES), can recruit the ribosome through a cap-independent mechanism. Translation from the IRES enables specialized regulation by the ribosome itself. For example, RPL38 is required for the translation of several TIE and IRES-containing Hox transcripts. These RNA elements are analogous to transcriptional enhancers and silencers (bottom), which act together to regulate gene expression.