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tRNA Activation02:26

tRNA Activation

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Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
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Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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Updated: Jul 6, 2025

High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry
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Selective gene expression maintains human tRNA anticodon pools during differentiation.

Lexi Gao1, Andrew Behrens1, Geraldine Rodschinka1

  • 1Mechanisms of Protein Biogenesis, Max Planck Institute of Biochemistry, Martinsried, Germany.

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|January 8, 2024
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Cell differentiation regulates transfer RNA (tRNA) expression by constraining RNA polymerase III transcription. This ensures stable tRNA anticodon pools, maintaining protein synthesis speed via mTORC1 signaling.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Transfer RNAs (tRNAs) are crucial for protein synthesis, translating genetic code.
  • The human genome has numerous tRNA genes, but their regulated expression is unclear.

Purpose of the Study:

  • To investigate tRNA expression regulation during human cell differentiation.
  • To understand how tRNA repertoires are controlled in neuronal and cardiac cells.

Main Methods:

  • Quantitative tRNA profiling.
  • Chromatin immunoprecipitation with sequencing (ChIP-seq).
  • Studied differentiation of human induced pluripotent stem cells (hiPSCs).

Main Results:

  • tRNA transcript levels varied significantly across differentiated cell types.
  • tRNA anticodon pools, critical for decoding rates, remained stable.
  • RNA polymerase III transcription shifted from broad to restricted (housekeeping tRNAs) upon differentiation.
  • This shift was linked to reduced mTORC1 signaling, activating MAF1.

Conclusions:

  • Cellular differentiation buffers tRNA anticodon pools to maintain consistent protein synthesis rates.
  • mTORC1 signaling plays a key role in selective tRNA gene expression during differentiation.