Abstract
Aberrant, misfolded, and mislocalized proteins are often toxic to cells and result in many human diseases. All proteins and their mRNA templates are subject to quality control. There are several distinct mechanisms that control the quality of mRNAs and proteins during translation at the ribosome. mRNA quality control systems, nonsense-mediated decay, non-stop decay, and no-go decay detect premature stop codons, the absence of a natural stop codon, and stalled ribosomes in translation, respectively, and degrade their mRNAs. Defective truncated polypeptide nascent chains generated from faulty mRNAs are degraded by ribosome-associated protein quality control pathways. Regulation of aberrant protein production, a novel pathway, senses aberrant proteins by monitoring the status of nascent chain interactions during translation and triggers degradation of their mRNA. Here, we review the current progress in understanding of the molecular mechanisms of mRNA and protein quality controls at the ribosome during translation.
Highlights
Genetic information is transferred during transcription and translation into correctly folded active proteins that are localized at the proper places for their functioning
When defective mRNAs and proteins are missed by these quality control systems, the aberrant proteins are degraded by proteolytic machinery in the cytosol (Heck et al, 2010), or in the endoplasmic reticulum (ER) by ER associated degradation (ERAD) pathway (Brodsky and Wojcikiewicz, 2009)
regulation of aberrant protein production (RAPP) senses mutated polypeptide nascent chains that are not able to interact with signal recognition particle (SRP) and are not targeted and not translocated into ER thereby reducing accumulation of these potentially hazardous proteins in the cytosol
Summary
Genetic information is transferred during transcription and translation into correctly folded active proteins that are localized at the proper places for their functioning. The regulation of aberrant protein production (RAPP) pathway senses aberrant proteins by scanning the status of nascent chains interactions mRNA and Protein Quality Controls during translation and triggers degradation of their mRNAs (Karamyshev et al, 2014; Pinarbasi et al, 2018). Large group of proteins involved in quality control and ubiquitination of aberrant nascent chains are found bound to translating ribosomes (Comyn et al, 2014).
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