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Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis
Published on: November 11, 2014
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A dual program for translation regulation in cellular proliferation and differentiation
Hila Gingold1, Disa Tehler2, Nanna R Christoffersen2
1Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Cell
|September 13, 2014
Summary
Two distinct transfer RNA (tRNA) subsets regulate cell proliferation and differentiation. These tRNA subsets coordinate with gene expression, suggesting distinct transcriptional programs for cell-autonomous and multicellular functions.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Metazoan cells face a fundamental choice between proliferation and differentiation.
- Transfer RNAs (tRNAs) are crucial for protein synthesis and can influence gene expression.
- Distinct cellular states may involve unique regulatory mechanisms for tRNA and gene expression.
Purpose of the Study:
- To investigate the relationship between tRNA pools and cellular states (proliferation vs. differentiation).
- To identify distinct codon usage patterns in genes associated with cell-autonomous functions and multicellularity.
- To explore the coordination between tRNA supply and gene transcription during these cellular processes.
Main Methods:
- Measurement of tRNA pools across various cell types.
- Analysis of codon usage in genes related to cell-autonomous functions and multicellularity.
- Examination of histone modifications near tRNA genes and their target genes.
Main Results:
- Identified two distinct tRNA subsets: one induced in proliferating cells, the other in differentiating cells.
- Found that cell-autonomous genes and multicellularity genes exhibit distinct codon usage.
- Observed coordinated changes in histone modifications near tRNA genes and their corresponding target genes, suggesting transcriptional regulation.
- Proliferation-induced tRNAs match codons enriched in cell-autonomous genes; differentiation-induced tRNAs match codons enriched in multicellularity genes.
Conclusions:
- Two distinct translational programs exist, operating during proliferation and differentiation.
- Transcriptional programs coordinate tRNA supply with the demand dictated by gene expression patterns.
- This coordination suggests a regulatory mechanism linking cell fate decisions to translational control.
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