Datasets

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

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

Kampen et al. 2019 (PRJNA417116)