Biological significance of nascent polypeptides that stall the ribosome

Abstract

The local speed of polypeptide elongation by the ribosome is not constant. One of the elements that modulate the rates of elongation or termination in translation is the amino acid sequence of the nascent polypeptide, the product of translation. Regulatory nascent polypeptides contain a segment that interacts with the ribosomal components from the peptidyl-transferase center (PTC) through the exit tunnel and arrests translation continuation beyond it. In many cases, translation arrest is either inducible with a specific effector molecule (such as a metabolite and an antibiotic) or subject to release by the engagement of the nascent peptide in a specific cellular event such as targeting and translocation. The stalling of the ribosome affects the cellular states of mRNA, leading to specific biological outputs, including induction or repression of target genes, recoding, and regulated mRNA localization in the cell. Arrest sequences are divergent in the amino acid sequences, and each of them interacts with the ribosome in a distinct way. Near the PTC, amino acids close to the arrest point interact with PTC-proximal residues of the large-subunit ribosomal RNA, whereas near the constricted region of the tunnel, more N-terminal amino acids of the nascent chain interact with ribosomal proteins L22 (also called L17 in eukaryotes) and L4, as well as with some ribosomal RNA residues. These interactions seem to create a specific configuration of the nascent chain and the ribosomal components to cis-specifically interfere with the translation reactions. Regulatory nascent polypeptides, which monitor cellular physiology and control gene expression in unique ways, have thus provided new concepts about the transformation of genetic information into cellular functions.