Translational read-through promotes aggregation and shapes stop codon identity

Nucleic Acids Research
Lior Kramarski, Eyal Arbely

Abstract

Faithful translation of genetic information depends on the ability of the translational machinery to decode stop codons as termination signals. Although termination of protein synthesis is highly efficient, errors in decoding of stop codons may lead to the synthesis of C-terminally extended proteins. It was found that in eukaryotes such elongated proteins do not accumulate in cells. However, the mechanism for sequestration of C-terminally extended proteins is still unknown. Here we show that 3'-UTR-encoded polypeptides promote aggregation of the C-terminally extended proteins, and targeting to lysosomes. We demonstrate that 3'-UTR-encoded polypeptides can promote different levels of protein aggregation, similar to random sequences. We also show that aggregation of endogenous proteins can be induced by aminoglycoside antibiotics that promote stop codon read-through, by UAG suppressor tRNA, or by knokcdown of release factor 1. Furthermore, we find correlation between the fidelity of termination signals, and the predicted propensity of downstream 3'-UTR-encoded polypeptides to form intrinsically disordered regions. Our data highlight a new quality control mechanism for elimination of C-terminally elongated proteins.

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Citations

Feb 11, 2021·Wiley Interdisciplinary Reviews. RNA·Joseph J PorterJohn D Lueck
Mar 7, 2021·International Journal of Molecular Sciences·Frida BelinkyIgor B Rogozin
Mar 26, 2021·Nucleic Acids Research·Alireza Baradaran-HeraviMichel Roberge

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Datasets Mentioned

BETA
PXD016728

Methods Mentioned

BETA
transfection
electrophoresis
confocal microscopy

Software Mentioned

SlideBook
TANGO
PylRS
Ensembl
PANTHR
ProteomeXchange
PANTHER
R
IUPred2A
Python

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Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.