ribofootPrinter: A precision python toolbox for analysis of ribosome profiling data

Guydosh, Nicholas R.

doi:10.1101/2021.07.04.451082

Cited by 2 publications

(2 citation statements)

References 29 publications

(32 reference statements)

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“…The output of the DEseq2 analysis for the RNA-seq and ribosome profiling are provided as Supplemental Table 1 and 2. For further analysis of individual genes, we computed TEs directly by dividing reads per million (rpm) values of ribosome profiling and RNA-seq by previously established pipelines in our lab (see more details in (Guydosh, 2021; Karasik et al ., 2021)). This allowed us to directly compare replicates within a treatment group.…”

Section: Methodsmentioning

confidence: 99%

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Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response

Karasik,

Lorenzi,

DePass

et al. 2023

Preprint

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SummaryDuring viral infection, several dsRNA sensors are activated in the cell and trigger signaling that leads to changes in gene expression. One of these sensors activates an endonuclease, RNase L, that cleaves many types of RNA in the cell. However, how the resultant widespread RNA decay affects gene expression is not fully understood. Here we found that gene expression changes caused by activating dsRNA sensing pathways are tuned by RNase L activation, pointing to intricacy in the innate immune response where multiple inputs are integrated to create an optimized output. We show that RNase-L-dependent RNA fragmentation induces the activation of the Ribotoxic Stress Response, potentially through ribosome collisions. The p38 and JNK pathways that are activated as part of this response promote outcomes that inhibit the virus, such as programmed cell death. We also show that RNase L appears to limit the translation of genes that are regulated by another dsRNA-induced pathway, the Integrated Stress Response. Intriguingly, we found the activity of the generic endonuclease, RNase A, recapitulates many of the same molecular phenotypes as activated RNase L, demonstrating how widespread RNA cleavage events can directly evoke an antiviral program.Key summaryActivated RNase L acts together with other dsRNA-sensing pathways to induce a strong immune response via JNK and p38 signalingGeneric RNA fragmentation plays a key role in inducing transcription, potentially through ribosome collisionsActivation of RNase L inhibits the effects of eIF2α phosphorylationTranslation of the antiviral IFIT mRNAs is inhibited by active RNase L

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Section: Methodsmentioning

confidence: 99%

“…For more detailed analysis of ribosome profiling data, we implemented a reduced-transcriptome alignment and python analysis pipeline as described elsewhere 21,86 . We used the Ref-Seq Select+MANE (ncbiRefSeqSelect), as downloaded from UCSC on 14 April 2020, for this alignment after removal of duplicates on alt chromosomes.…”

Section: Computational Analysismentioning

confidence: 99%

Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response

Karasik,

Lorenzi,

DePass

et al. 2023

Preprint

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mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations

Gasparski

Moissoglu

Pallikkuth

et al. 2023

Preprint

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Numerous proteins are targeted to two or multiple subcellular destinations where they exert distinct functional consequences. The balance between such differential targeting is thought to be determined post-translationally, relying on protein sorting mechanisms. Here, we show that protein targeting can additionally be determined by mRNA location and translation rate, through modulating protein binding to specific interacting partners. Peripheral localization of the NET1 mRNA and fast translation lead to higher cytosolic retention of the NET1 protein, through promoting its binding to the membrane-associated scaffold protein CASK. By contrast, perinuclear mRNA location and/or slower translation rate favor nuclear targeting, through promoting binding to importins. This mRNA location-dependent mechanism is modulated by physiological stimuli and profoundly impacts NET1 function in cell motility. These results reveal that the location of protein synthesis and the rate of translation elongation act in coordination as a "partner-selection" mechanism that robustly influences protein distribution and function.

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ribofootPrinter: A precision python toolbox for analysis of ribosome profiling data

Cited by 2 publications

References 29 publications

Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response

Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response

mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations

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