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Dynamic remodeling of mRNA splicing and translation programs drives hepatocyte proliferation during liver regeneration

ABSTRACT: During liver regeneration, most new hepatocytes arise from pre-existing ones; yet, the underlying mechanisms that drive these cells from quiescence to proliferation remain poorly defined. By using high-resolution transcriptome profiling of purified hepatocytes isolated from quiescent and toxin-injured adult mouse livers,we uncover an overlap of regenerative response with developmental transcriptome programming. The translational remodeling modulates protein levels ofa set of splicing factors including Epithelial splicing regulatory protein 2 (ESRP2), which activates an early postnatal splicing program in regenerating hepatocytes. We find that regeneration-regulated exons are enriched within unstructured regions of proteins and frequently harbor amino-acid residues that can be post-translationally modified to influence protein-protein interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE105944 | GEO | 2018/09/17

REPOSITORIES: GEO

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Dynamic remodeling of translation programs drives hepatocyte proliferation during liver regeneration

Project description:During liver regeneration, most new hepatocytes arise from pre-existing ones; yet, the underlying mechanisms that drive these cells from quiescence to proliferation remain poorly defined. By using high-resolution transcriptome profiling of polysome fractions from purified hepatocytes isolated from quiescent and toxin-injured adult mouse livers,we uncover the mRNA transcripts regulated during liver regeneration. The translational remodeling modulates protein levels of a set of splicing factors including Epithelial splicing regulatory protein 2 (ESRP2), which activates an early postnatal splicing program in regenerating hepatocytes as well as metabolic genes.

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RNA-sequencing in OS-RC-2 cells under the knockdown of Arkadia or ESRP2

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