riboWaltz: optimization of ribosome P-site positioning in ribosome profiling data

Lauria, Fabio; Tebaldi, Toma; Bernabò, Paola; Groen, Ewout J N; Gillingwater, Thomas H.; Viero, Gabriella

doi:10.1101/169862

Cited by 23 publications

(28 citation statements)

References 28 publications

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“…3F) or RDO at optimal codons; instead it displayed increased RDO at proline CCA codon, related to eIF5a function in facilitating elongation at proline codons (12,16). Comparison of RPF changes between wild type and not5Δ to those in newly synthesized proteins selected from a SILAC analysis (8) showed an 25 overall good correlation (Fig. 3D), indicating that the detected RPF changes in not5Δ (Fig.…”

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confidence: 82%

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Switch from translation initiation to elongation needs Not4 and Not5 collaboration

Allen

Panasenko

Villányi

et al. 2019

Preprint

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Not4 and Not5 are crucial components of the Ccr4-Not complex with pivotal functions in mRNA metabolism. Both associate with ribosomes but mechanistic insights on their function remain elusive. Here we determine that Not5 and Not4 synchronously impact translation initiation and Not5 alone alters translation elongation. Deletion of Not5 causes elongation defects in a codon-dependent fashion, increasing and decreasing the ribosome dwelling occupancy at minor and major codons, respectively. This larger difference in codons’ translation velocities alters translation globally and enables kinetically unfavorable processes such as nascent chain deubiquitination to take place. In turn, this leads to abortive translation and favors protein aggregation. These findings highlight the global impact of Not4 and Not5 in controlling the speed of mRNA translation and transition from initiation to elongation.SummaryNot4 and Not5 regulate translation synchronously but distinguishably, facilitating smooth transition from initiation to elongation

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confidence: 82%

“…S1F). 25 The concentration of the cognate aminoacyl-tRNA is one major determinant of the ribosome speed at a codon in the ribosome A-site. We measured the concentrations of total and aminoacylated tRNAs using tRNA-tailored microarrays.…”

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confidence: 99%

Switch from translation initiation to elongation needs Not4 and Not5 collaboration

Allen

Panasenko

Villányi

et al. 2019

Preprint

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“…Figure 10L). We applied riboWaltz (41), an R package to calculate the P-site offset and perform the diagnostic analysis/inspection of the ribosomal profiling data. We examined the percentage of P-sites falling in the three annotated transcript regions (5' UTR, CDS and 3' UTR), which revealed that the majority of the ribosome footprint reads were in CDS ( Figure 7F).…”

Section: Transcriptome(mrna-seq) Data Analysismentioning

confidence: 99%

Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis

Uyhazi

Yang

Liu

et al. 2019

Preprint

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Gene regulation in embryonic stem cells (ESCs) has been extensively studied at the epigenetic-transcriptional levels, but not at the post-transcriptional levels. Pumilio (Pum) proteins are among the few known translational regulators required for stem cell maintenance in invertebrates and plants. Here we report the essential function of two murine Pum proteins, Pum1 and Pum2, in ESCs and early embryogenesis. Pum1/2 double mutants are developmentally delayed at the morula stage and lethal by embryonic day 8.5 (e8.5).Correspondingly, Pum1/2 double mutant ESCs display severely reduced self-renewal and differentiation, revealing the combined function of Pum1 and Pum2 in ESC pluripotency.Remarkably, Pum1-deficient ESCs show increased expression of pluripotency genes but not differentiation genes, indicating that Pum1 mainly promote differentiation; whereas Pum2deficient ESCs show decreased expression of pluripotency genes and accelerated differentiation, indicating that Pum2 promotes self-renewal. Thus, Pum1 and Pum2 each uniquely contributes to one of the two complementary aspects of pluripotency. Furthermore, we show that Pum1 and Pum2 achieve ESC functions by forming a negative auto-and inter-regulatory feedback loop that directly regulates at least 1,486 mRNAs. Pum1 and Pum2 regulate target mRNAs not only by repressing translation as expected but also by promoting translation and enhancing or reducing mRNA stability of different target mRNAs. Together, these findings reveal the distinct roles of individual mammalian Pum proteins in ESCs and their collectively essential functions in ESC pluripotency and embryogenesis. Moreover, they demonstrate three novel modes of regulation of Pum proteins towards target mRNAs.

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“…Therefore, in bacteria, an offset of 12 nucleotides from the 3 end of the read is used to infer the A-site (Martens, Taylor, & Hilser, 2015;Woolstenhulme, Guydosh, Green, & Buskirk, 2015). A number of publicly available tools now exist for determining a refined offset for individual read lengths such as Plastid (Dunn & Weissman, 2016), Ri-boWaltz, (Lauria et al, 2017), RP-BP (Malone et al, 2017), and RiboProfiling (Popa et al, 2016). We hope to soon incorporate a similar approach into the GWIPS-viz computational pipeline that assigns offset values for individual read lengths.…”

Section: Of 24mentioning

confidence: 99%

The GWIPS‐viz Browser

Kiniry

Michel

Baranov

2018

CP in Bioinformatics

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GWIPS-viz is a publicly available browser that provides Genome Wide Information on Protein Synthesis through the visualization of ribosome profiling data. Ribosome profiling (Ribo-seq) is a high-throughput technique which isolates fragments of messenger RNA that are protected by the ribosome. The alignment of the ribosome-protected fragments or footprint sequences to the corresponding reference genome and their visualization using GWIPS-viz allows for unique insights into the genome loci that are expressed as potentially translated RNA. The GWIPS-viz browser hosts both Ribo-seq data and corresponding mRNA-seq data from publicly available studies across a number of genomes, avoiding the need for computational processing on the user side. Since its initial publication in 2014, over 1885 tracks have been produced across 24 genomes. This unit describes the navigation of the GWIPS-viz genome browser, the uploading of custom tracks, and the downloading of the Ribo-seq/mRNA-seq alignment data. © 2018 by John Wiley & Sons, Inc.

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riboWaltz: optimization of ribosome P-site positioning in ribosome profiling data

Cited by 23 publications

References 28 publications

Switch from translation initiation to elongation needs Not4 and Not5 collaboration

Switch from translation initiation to elongation needs Not4 and Not5 collaboration

Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis

The GWIPS‐viz Browser

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