Kampen et al. 2019 (PRJNA417116)

General Details

Title Translatome analysis of the ribosomal protein L10 R98S mutation reveals altered serine metabolism in acute lymphoblastic leukemia [Ribo-seq]
Organism
Number of Samples 24
Release Date 2017/11/03 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP123624
ENA SRP123624
GEO
BioProject PRJNA417116

Publication

Title
Authors Kampen KR,Fancello L,Girardi T,Rinaldi G,Planque M,Sulima SO,Loayza-Puch F,Verbelen B,Vereecke S,Verbeeck J,Op de Beeck J,Royaert J,Vermeersch P,Cassiman D,Cools J,Agami R,Fiers M,Fendt SM,De Keersmaecker K
Journal Nature communications
Publication Date 2019 Jun 11
Abstract Somatic ribosomal protein mutations have recently been described in cancer, yet their impact on cellular transcription and translation remains poorly understood. Here, we integrate mRNA sequencing, ribosome footprinting, polysomal RNA sequencing and mass spectrometry datasets from a mouse lymphoid cell model to characterize the T-cell acute lymphoblastic leukemia (T-ALL) associated ribosomal RPL10 R98S mutation. Surprisingly, RPL10 R98S induces changes in protein levels primarily through transcriptional rather than translation efficiency changes. Phosphoserine phosphatase (PSPH), encoding a key serine biosynthesis enzyme, was the only gene with elevated transcription and translation leading to protein overexpression. PSPH upregulation is a general phenomenon in T-ALL patient samples, associated with elevated serine and glycine levels in xenograft mice. Reduction of PSPH expression suppresses proliferation of T-ALL cell lines and their capacity to expand in mice. We identify ribosomal mutation driven induction of serine biosynthesis and provide evidence supporting dependence of T-ALL cells on PSPH.
PMC PMC6559966
PMID 31186416
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR6255560 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255561 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255562 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255563 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255564 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255565 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255566 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255567 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255568 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255569 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255570 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255571 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255572 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255573 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255574 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255575 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255576 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255577 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255578 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255579 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255580 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255581 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255582 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
SRR6255583 PRJNA417116 Mus musculus mouse lymphoid Ba/F3 cells Ribo-Seq
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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