Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control

Abstract

Assembly of fully functional ribosomes is a prerequisite for failsafe translation. This explains why maturing preribosomal subunits have to pass through an array of quality-control checkpoints, including nuclear export, to ensure that only properly assembled ribosomes engage in translation. Despite these safeguards, we found that nuclear pre-60S particles unable to remove a transient structure composed of ITS2 pre-rRNA and associated assembly factors, termed the 'foot', escape to the cytoplasm, where they can join with mature 40S subunits to catalyze protein synthesis. However, cells harboring these abnormal ribosomes show translation defects indicated by the formation of 80S ribosomes poised with pre-60S subunits carrying tRNAs in trapped hybrid states. To overcome this translational stress, the cytoplasmic surveillance machineries RQC and Ski-exosome target these malfunctioning ribosomes. Thus, pre-60S subunits that escape nuclear quality control can enter translation, but are caught by cytoplasmic surveillance mechanisms.

Assembly of the small ribosomal subunit in yeast: mechanism and regulation

“…This would be consistent with this step being an important checkpoint in the quality control of the nascent 40S. Faulty 60S subunits that contain an unprocessed ITS2 were shown to be targeted by the nonsense-mediated decay machinery (Sarkar et al 2017). This may provide us with a clue of what is likely to happen with defective 40S.…”

The small and large ribosomal subunits depend on each other for stability and accumulation

“…Some of the fragmented rRNA in the 60S peak hybridizes to the transcribed spacer probes. Processing of 25S rRNA is believed to be complete prior to nuclear export, but precursor 60S particles containing ITS2 can escape to the cytoplasm during impaired ITS2 processing (Sarkar et al 2017). We speculate that nuclear processing of pre-25S rRNA may be subtly distorted in the absence of 40S assembly, even though the 40S and 60S assembly pathways are believed to be largely independent.…”

“…We speculate that nuclear processing of pre-25S rRNA may be subtly distorted in the absence of 40S assembly, even though the 40S and 60S assembly pathways are believed to be largely independent. Cytoplasmic pre-60S particles form defective 80S ribosomes that are degraded (Sarkar et al 2017), but it is conceivable that they can also be degraded if they fail to form 80S couples due to the deficiency in the number of 40S subunits. As suggested above for the 40S subunit, the 60S interface side could be vulnerable to nucleases in the absence of the 40S partner.…”

Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes

“…Ribosomes are synthesized as ribosomal subunits in the nucleus and function as decoding machines in the cytoplasm. Their functionality is proved and defective ribosomes are eliminated by the ribosome quality control (RQC) (Sarkar et al, 2017). Similarly, aberrantly processed mRNAs are detected in the nucleus by the guard proteins that initiate faulty mRNA degradation (Zander et al, 2016;Zander and Krebber, 2017).…”