A cellular handbook for collided ribosomes: surveillance pathways and collision types
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REVIEW
A cellular handbook for collided ribosomes: surveillance pathways and collision types Sezen Meydan1,2 · Nicholas R. Guydosh1 Received: 12 September 2020 / Revised: 12 September 2020 / Accepted: 18 September 2020 © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
Abstract Translating ribosomes slow down or completely stall when they encounter obstacles on mRNAs. Such events can lead to ribosomes colliding with each other and forming complexes of two (disome), three (trisome) or more ribosomes. While these events can activate surveillance pathways, it has been unclear if collisions are common on endogenous mRNAs and whether they are usually detected by these cellular pathways. Recent genome-wide surveys of collisions revealed widespread distribution of disomes and trisomes across endogenous mRNAs in eukaryotic cells. Several studies further hinted that the recognition of collisions and response to them by multiple surveillance pathways depend on the context and duration of the ribosome stalling. This review considers recent efforts in the identification of endogenous ribosome collisions and cellular pathways dedicated to sense their severity. We further discuss the potential role of collided ribosomes in modulating cotranslational events and contributing to cellular homeostasis. Keywords Ribosome collisions · Disome · Trisome · Ribosome profiling · Surveillance pathway · Programmed ribosome stalling
Introduction Many kinds of impediments to translation can interrupt the movement of the ribosome, such as unfavorable codons, problematic amino acid sequences, downstream secondary structures or damaged mRNAs (Chandrasekaran et al. 2019; Doma and Parker 2006; Gamble et al. 2016; Letzring et al. 2013; Simms et al. 2014). Unresolved ribosome stalling has been linked to proteotoxicity and neurodegeneration (Choe et al. 2016; Chu et al. 2009; Nedialkova and Leidel 2015; Yonashiro et al. 2016), suggesting that severely slowed ribosomes must be detected and removed from the mRNA (“rescued”) to maintain cellular homeostasis. For this purpose, cells have evolved surveillance mechanisms that are Communicated by M. Kupiec. * Nicholas R. Guydosh [email protected] 1
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive Room 220, Bethesda, MD 20892, USA
National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD 20892, USA
2
responsible for recognizing and resolving aberrant ribosome stalling events, such as the Ribosome-associated Quality Control (RQC) system in eukaryotes (reviewed in Brandman and Hegde 2016; Joazeiro 2019). This recognition has been shown to occur via the specific detection of disomes or trisomes, which form due to prolonged ribosome stalling that signals a potentially detrimental translation slowdown (Ikeuchi et al. 2019; Juszkiewicz et al. 2018; Matsuo et al. 2020; Simms et al. 2017). Ribosome collisions are detected by an E
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