Translation of poly(A) tails leads to precise mRNA cleavage

Guydosh, Nicholas R.; Green, Rachel

doi:10.1261/rna.060418.116

Cited by 87 publications

(99 citation statements)

References 60 publications

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“…Third, and arguably most interesting, is the observation that cleavage takes place significantly in frame (Figure 2C, S2). This latter observation is similar to what has been observed recently using ribosomal profiling (Guydosh and Green, 2017) and suggests that the endonuclease is using the ribosome as a ruler. Consistent with this proposal, smoothing of the (CGA) 12 mapping data revealed a regular oscillation of read peaks with a median period of 29-nt (Figure 2B, 2D) and a tight distribution (standard deviation of 2.5-nt).…”

Section: Resultssupporting

confidence: 90%

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Ribosome Collision Is Critical for Quality Control during No-Go Decay

2017

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SUMMARY No-go decay (NGD) is a eukaryotic quality control mechanism that evolved to cope with translational arrests. The process is characterized by an endonucleolytic cleavage near the stall sequence, but the mechanistic details are unclear. Our analysis of cleavage sites indicates that cleavage requires multiple ribosomes on the mRNA. We also show that reporters harboring stall sequences near the initiation codon, which cannot accommodate multiple ribosomes, are not subject to NGD. Consistent with our model, we uncover an inverse correlation between ribosome density per mRNA and cleavage efficiency. Furthermore, promoting global ribosome collision in vivo resulted in ubiquitination of ribosomal proteins suggesting that collision is sensed by the cell to initiate downstream quality control processes. Collectively our data suggests that NGD and subsequent quality control are triggered by ribosome collision. This model provides insight into the regulation of quality control processes and the manner by which they reduce off target effects.

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Section: Resultssupporting

confidence: 90%

“…Our observations, as well as those of others, of the ~30-nt gaps between mapped cleavage products suggest that it is ribosome associated (Guydosh and Green, 2017). Our proposal of activation through ribosome collision offers an elegant mechanism for its regulation.…”

Section: Discussionsupporting

confidence: 89%

Ribosome Collision Is Critical for Quality Control during No-Go Decay

2017

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“…In addition to splitting ribosomes at the extreme end of transcripts, Dom34 has been shown to dissociate ribosomes stalled at poly-lysine sequences within the poly(A) tail (Guydosh and Green 2014) and within the ORF (Guydosh and Green 2017). Further work will be needed to determine the stall types that each of these splitting modes preferentially responds to in order to generate substrates for the RQC.…”

Section: ) Withoutmentioning

confidence: 99%

Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation

Sitron

Park

Brandman

2017

RNA

127

150

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Premature arrest of protein synthesis within the open reading frame elicits a protective response that degrades the incomplete nascent chain. In this response, arrested 80S ribosomes are split into their large and small subunits, allowing assembly of the ribosome quality control complex (RQC), which targets nascent chains for degradation. How the cell recognizes arrested nascent chains among the vast pool of actively translating polypeptides is poorly understood. We systematically examined translation arrest and modification of nascent chains in Saccharomyces cerevisiae to characterize the steps that couple arrest to RQC targeting. We focused our analysis on two poorly understood 80S ribosome-binding proteins previously implicated in the response to failed translation, Asc1 and Hel2, as well as a new component of the pathway, Slh1, that we identified here. We found that premature arrest at ribosome stalling sequences still occurred robustly in the absence of Asc1, Hel2, and Slh1. However, these three factors were required for the RQC to modify the nascent chain. We propose that Asc1, Hel2, and Slh1 target arresting ribosomes and that this targeting event is a precondition for the RQC to engage the incomplete nascent chain and facilitate its degradation.

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“…In contrast, recent work revealed that RPF lengths are variable and carry critical information (Lareau et al, 2014;Wu et al, 2019;Liakath-Ali et al, 2018). For example, ribosomes can protect short footprints (15-21 nts), characteristic of different ribosome conformations (Guydosh and Green, 2017;Lareau et al, 2014;Wu et al, 2019), as well as longer footprints (~60 nt) indicative of ribosome collisions (Arpat et al;Guydosh and Green, 2014). Importantly, these key observations signal a new chapter of translation studies that will need to be analyzed by taking variable RPF lengths into account.…”

Section: Introductionmentioning

confidence: 99%

RiboFlow, RiboR and RiboPy: An ecosystem for analyzing ribosome profiling data at read length resolution

Özadam

Geng

Cenik

2019

Preprint

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Ribosome occupancy measurements enable protein abundance estimation and infer mechanisms of translation. Recent studies have revealed that sequence read lengths in ribosome profiling data are highly variable and carry critical information. Consequently, data analyses require the computation and storage of multiple metrics for a wide range of ribosome footprint lengths. We developed a software ecosystem including a new efficient binary file format named 'ribo'. Ribo files store all essential data grouped by ribosome footprint lengths. Users can assemble ribo files using our RiboFlow pipeline that processes raw ribosomal profiling sequencing data. RiboFlow is highly portable and customizable across a large number of computational environments with built-in capabilities for parallelization. We also developed interfaces for writing and reading ribo files in the R (RiboR) and Python (RiboPy) environments. Using RiboR and RiboPy, users can efficiently access ribosome profiling quality control metrics, generate essential plots, and carry out analyses. Altogether, these components create a complete software ecosystem for researchers to study translation through ribosome profiling. Availability and ImplementationFor a quickstart, please see https://ribosomeprofiling.github.io. Source code, installation instructions and links to documentation are available on GitHub: https://github.com/ribosomeprofiling

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Translation of poly(A) tails leads to precise mRNA cleavage

Cited by 87 publications

References 60 publications

Ribosome Collision Is Critical for Quality Control during No-Go Decay

Ribosome Collision Is Critical for Quality Control during No-Go Decay

Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation

RiboFlow, RiboR and RiboPy: An ecosystem for analyzing ribosome profiling data at read length resolution

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