Assembly Defects Abrogate Proofreading by Initiation Factors and License the Entry of Premature Ribosomes into the Translation Cycle

Abstract

Numerous quality control steps are deployed by the translational machinery to ensure faithful decoding of genetic message to synthesize proteins. However, what transpires to quality control mechanism during protein synthesis when the ribosomes are produced with assembly defects remains enigmatic. In E. coli, we show that ribosomes with assembly defects evade the proofreading steps during translation initiation and participate in the translation cycle. Such ribosomes show severely compromised decoding capabilities that give rise to errors in initiation and elongation. Tracing the genesis, we discovered that the assembly defects compromise the binding of initiation factors, thus licensing the rapid transitioning of 30S (pre) initiation complex to 70S initiation complex by tempering the proofreading mechanism. Overall, our work highlights that a mass balance deficit between premature ribosomes and initiation factors steers the entry of premature ribosomes into the translation cycle.