scholarly journals Ribosome pausing, arrest and rescue in bacteria and eukaryotes

2017 ◽  
Vol 372 (1716) ◽  
pp. 20160183 ◽  
Author(s):  
Allen R. Buskirk ◽  
Rachel Green
Keyword(s):  
Quality Control ◽  
Protein Synthesis ◽  
Control Systems ◽  
Genetic Information ◽  
Ribosome Profiling ◽  
Molecular Events ◽  
Similarities And Differences ◽  
Ribosome Pausing

Ribosomes translate genetic information into polypeptides in several basic steps: initiation, elongation, termination and recycling. When ribosomes are arrested during elongation or termination, the cell's capacity for protein synthesis is reduced. There are numerous quality control systems in place to distinguish between paused ribosomes that need some extra input to proceed and terminally stalled ribosomes that need to be rescued. Here, we discuss similarities and differences in the systems for resolution of pauses and rescue of arrested ribosomes in bacteria and eukaryotes, and how ribosome profiling has transformed our ability to decipher these molecular events. This article is part of the themed issue ‘Perspectives on the ribosome’.

scholarly journals Genome-wide survey of ribosome collision

2019 ◽  
Author(s):  
Peixun Han ◽  
Mari Mito ◽  
Yuichi Shichino ◽  
Satoshi Hashimoto ◽  
Tsuyoshi Udagawa ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Profiling ◽  
Unfolded Protein ◽  
Genome Wide ◽  
A Genome ◽  
The Unfolded Protein Response ◽  
Ribosome Pausing ◽  
Protein Response ◽  
Insight Into ◽  
Genome Wide Survey

AbstractIn protein synthesis, ribosome movement is not always smooth and is rather often impeded for numerous reasons. Although the deceleration of the ribosome defines the fates of the mRNAs and synthesizing proteins, fundamental issues remain to be addressed, including where ribosomes pause in mRNAs, what kind of RNA/amino acid sequence causes this pause, and the physiological significance of this slowdown of protein synthesis. Here, we surveyed the positions of ribosome collisions caused by ribosome pausing in humans and zebrafish on a genome-wide level using modified ribosome profiling. The collided ribosomes, i.e., disomes, emerged at various sites: the proline-proline-lysine motif, stop codons, and the 3′ untranslated region (UTR). The number of ribosomes involved in a collision is not limited to two, but rather four to five ribosomes can form a queue of ribosomes. In particular, XBP1, a key modulator of the unfolded protein response, shows striking queues of collided ribosomes and thus acts as a substrate for ribosome-associated quality control (RQC) to avoid the accumulation of undesired proteins in the absence of stress. Our results provide an insight into the causes and consequences of ribosome slowdown by dissecting the specific architecture of ribosomes.

scholarly journals Quality controls induced by aberrant translation

2020 ◽  
Vol 48 (3) ◽  
pp. 1084-1096 ◽  
Author(s):  
Toshifumi Inada
Keyword(s):  
Quality Control ◽  
Protein Synthesis ◽  
Cell Viability ◽  
Control Systems ◽  
Polypeptide Chain ◽  
Translation Product ◽  
Regulatory Factors ◽  
Nascent Polypeptide ◽  
Quality Controls ◽  
Ribosome Stalling

Abstract During protein synthesis, translating ribosomes encounter many challenges imposed by various types of defective mRNAs that can lead to reduced cellular fitness and, in some cases, even threaten cell viability. Aberrant translation leads to activation of one of several quality control pathways depending on the nature of the problem. These pathways promote the degradation of the problematic mRNA as well as the incomplete translation product, the nascent polypeptide chain. Many of these quality control systems feature critical roles for specialized regulatory factors that work in concert with conventional factors. This review focuses on the mechanisms used by these quality control pathways to recognize aberrant ribosome stalling and discusses the conservation of these systems.

scholarly journals Cell-free protein synthesis and in situ immobilization of deGFP-MatB in polymer microgels for malonate-to-malonyl CoA conversion

RSC Advances ◽  
2020 ◽  
Vol 10 (66) ◽  
pp. 40588-40596
Author(s):  
Tony Köhler ◽  
Thomas Heida ◽  
Sandra Hoefgen ◽  
Niclas Weigel ◽  
Vito Valiante ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Genetic Information ◽  
In Situ Immobilization ◽  
Bottom Up ◽  
Free Protein ◽  
Malonyl Coa ◽  
Cell Free Protein Synthesis

We describe a bottom-up approach towards functional enzymes utilizing microgels as carriers for genetic information that enable cell-free protein synthesis, in situ immobilization, and utilization of functional deGFP-MatB.

scholarly journals Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.

scholarly journals 40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David J. Young ◽  
Sezen Meydan ◽  
Nicholas R. Guydosh
Keyword(s):  
Protein Synthesis ◽  
Neurological Disease ◽  
Ribosome Profiling ◽  
Minor Role ◽  
Stop Codons ◽  
Genes Encoding ◽  
Ribosome Footprinting ◽  
A Minor ◽  
And Control ◽  
In Cells

AbstractThe recycling of ribosomes at stop codons for use in further rounds of translation is critical for efficient protein synthesis. Removal of the 60S subunit is catalyzed by the ATPase Rli1 (ABCE1) while removal of the 40S is thought to require Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR). However, it remains unclear how these Tma proteins cause 40S removal and control reinitiation of downstream translation. Here we used a 40S ribosome footprinting strategy to directly observe intermediate steps of ribosome recycling in cells. Deletion of the genes encoding these Tma proteins resulted in broad accumulation of unrecycled 40S subunits at stop codons, directly establishing their role in 40S recycling. Furthermore, the Tma20/Tma22 heterodimer was responsible for a majority of 40S recycling events while Tma64 played a minor role. Introduction of an autism-associated mutation into TMA22 resulted in a loss of 40S recycling activity, linking ribosome recycling and neurological disease.

scholarly journals A freestanding proofreading domain is required for protein synthesis quality control in Archaea

2004 ◽  
Vol 101 (28) ◽  
pp. 10260-10265 ◽  
Author(s):  
D. Korencic ◽  
I. Ahel ◽  
J. Schelert ◽  
M. Sacher ◽  
B. Ruan ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Synthesis

scholarly journals Protein synthesis persists during necrotic cell death

2005 ◽  
Vol 168 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Xavier Saelens ◽  
Nele Festjens ◽  
Eef Parthoens ◽  
Isabel Vanoverberghe ◽  
Michael Kalai ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
De Novo ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Proteolytic Activation ◽  
Double Stranded Rna ◽  
Molecular Events

Cell death is an intrinsic part of metazoan development and mammalian immune regulation. Whereas the molecular events orchestrating apoptosis have been characterized extensively, little is known about the biochemistry of necrotic cell death. Here, we show that, in contrast to apoptosis, the induction of necrosis does not lead to the shut down of protein synthesis. The rapid drop in protein synthesis observed in apoptosis correlates with caspase-dependent breakdown of eukaryotic translation initiation factor (eIF) 4G, activation of the double-stranded RNA-activated protein kinase PKR, and phosphorylation of its substrate eIF2-α. In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-α phosphorylation, and proteolytic activation of PKR are absent. Collectively, these results show that, in contrast to apoptotic cells, necrotic dying cells retain the opportunity to synthesize proteins.

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