Bachelor of Arts, Harvard University (2011)
Doctor of Philosophy, Massachusetts Institute of Technology (2016)
A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production.
2022; 13 (1): 5491
Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types or control cell fate remains unknown. Here, employing quantitative mass spectrometry during human embryonic stem cell differentiation, we identify dozens of ribosome composition changes underlying cell fate specification. We observe upregulation of RPL10A/uL1-containing ribosomes in the primitive streak followed by progressive decreases during mesoderm differentiation. An Rpl10a loss-of-function allele in mice causes striking early mesodermal phenotypes, including posterior trunk truncations, and inhibits paraxial mesoderm production in culture. Ribosome profiling in Rpl10a loss-of-function mice reveals decreased translation of mesoderm regulators, including Wnt pathway mRNAs, which are also enriched on RPL10A/uL1-containing ribosomes. We further show that RPL10A/uL1 regulates canonical and non-canonical Wnt signaling during stem cell differentiation and in the developing embryo. These findings reveal unexpected ribosome composition modularity that controls differentiation and development through the specialized translation of key signaling networks.
View details for DOI 10.1038/s41467-022-33263-3
View details for PubMedID 36123354
Tag-free rapid enrichment of ribosome-associated proteins across cell types, tissues, and species
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. 2019: S78
View details for Web of Science ID 000516535000127
Characterizing the role of ribosomal protein phosphorylation in control of gene regulation and cell fate
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. 2019: S77
View details for Web of Science ID 000516535000125
Ribosome Heterogeneity in Translating the Genetic Code
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. 2019: S23
View details for Web of Science ID 000516535000018
Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in living human cells by proximity biotinylation
The cytosol-facing membranes of cellular organelles contain proteins that enable signal transduction, regulation of morphology and trafficking, protein import and export, and other specialized processes. Discovery of these proteins by traditional biochemical fractionation can be plagued with contaminants and loss of key components. Using peroxidase-mediated proximity biotinylation, we captured and identified endogenous proteins on the outer mitochondrial membrane (OMM) and endoplasmic reticulum membrane (ERM) of living human fibroblasts. The proteomes of 137 and 634 proteins, respectively, are highly specific and highlight 94 potentially novel mitochondrial or ER proteins. Dataset intersection identified protein candidates potentially localized to mitochondria-ER contact sites. We found that one candidate, the tail-anchored, PDZ-domain-containing OMM protein SYNJ2BP, dramatically increases mitochondrial contacts with rough ER when overexpressed. Immunoprecipitation-mass spectrometry identified ribosome-binding protein 1 (RRBP1) as SYNJ2BP's ERM binding partner. Our results highlight the power of proximity biotinylation to yield insights into the molecular composition and function of intracellular membranes.
View details for DOI 10.7554/eLife.24463
View details for Web of Science ID 000400017500001
View details for PubMedID 28441135
View details for PubMedCentralID PMC5404927