Liakath-Ali et al. 2017 (PRJNA369542)

General Details

Title Ribosome profiling and RNA-Sequencing of wild type and Pelota knockout mouse epidermis
Organism
Number of Samples 7
Release Date 2017/02/01 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP098700
ENA SRP098700
GEO
BioProject PRJNA369542

Publication

Title
Authors Liakath-Ali K,Mills EW,Sequeira I,Lichtenberger BM,Pisco AO,Sipilä KH,Mishra A,Yoshikawa H,Wu CC,Ly T,Lamond AI,Adham IM,Green R,Watt FM
Journal Nature
Publication Date 2018 Apr
Abstract Ribosome-associated mRNA quality control mechanisms ensure the fidelity of protein translation 1,2 . Although these mechanisms have been extensively studied in yeast, little is known about their role in mammalian tissues, despite emerging evidence that stem cell fate is controlled by translational mechanisms 3,4 . One evolutionarily conserved component of the quality control machinery, Dom34 (in higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes 5 . Here we show that Pelo is required for mammalian epidermal homeostasis. Conditional deletion of Pelo in mouse epidermal stem cells that express Lrig1 results in hyperproliferation and abnormal differentiation of these cells. By contrast, deletion of Pelo in Lgr5-expressing stem cells has no effect and deletion in Lgr6-expressing stem cells induces only a mild phenotype. Loss of Pelo results in accumulation of short ribosome footprints and global upregulation of translation, rather than affecting the expression of specific genes. Translational inhibition by rapamycin-mediated downregulation of mTOR (mechanistic target of rapamycin kinase) rescues the epidermal phenotype. Our study reveals that the ribosome-rescue machinery is important for mammalian tissue homeostasis and that it has specific effects on different stem cell populations.
PMC
PMID 29643507
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR5223059 PRJNA369542 Mus musculus Ribo-Seq Cycloheximide
SRR5223060 PRJNA369542 Mus musculus Ribo-Seq Cycloheximide
SRR5223061 PRJNA369542 Mus musculus Ribo-Seq Cycloheximide
SRR5223062 PRJNA369542 Mus musculus Ribo-Seq Cycloheximide
SRR5223063 PRJNA369542 Mus musculus RNA-Seq Cycloheximide
SRR5223064 PRJNA369542 Mus musculus RNA-Seq Cycloheximide
SRR5223065 PRJNA369542 Mus musculus RNA-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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