Quick or quality? How mRNA escapes nuclear quality control during stress

Abstract

Understanding the mechanisms for mRNA production under normal conditions and in response to cytotoxic stresses has been subject of numerous studies for several decades. The shutdown of canonical mRNA transcription, export and translation is required to have enough free resources for the immediate production of heat shock proteins that act as chaperones to sustain cellular processes. In recent work we uncovered a simple mechanism, in which the export block of regular mRNAs and a fast export of heat shock mRNAs is achieved by deactivation of the nuclear mRNA quality control mediated by the guard proteins. In this point of view we combine long known data with recently gathered information that support this novel model, in which cells omit quality control of stress responsive transcripts to ensure survival.

Keywords: Heat stress; cellular stress; mRNA quality control; nuclear export.

Figure 1.

Guard proteins control mRNA maturation and nuclear export. Every maturation step results in association of guard proteins that recruit the export receptor Mex67-Mtr2 to the correct mRNA and support degradation by the TRAMP/exosome pathway for faulty transcripts. Finally, Mlp1 controls proper Mex67 decoration of the guard proteins to allow nuclear export.

Figure 2.

Stress conditions lead to dissociation of Mex67-complexes and a subsequent mRNA export block. Upon stress housekeeping mRNAs are no longer transcribed and Mex67 is dissociated with the guard proteins from mature mRNAs. The recruitment of the guard proteins is prevented by mechanisms, including phosphorylation, aggregation and foci-formation of guard proteins and the NPC gatekeeper Mlp1.

Figure 3.

Export of HS RNAs. Direct co-transcriptional recruitment of Mex67 to HS mRNAs allows omission of quality control and fast HS mRNA export.