Questions and Answers
What is the role of Drosha in miRNA biogenesis?
Drosha initiates the miRNA biogenesis process.
How does the newly identified Drosha isoform differ in expression compared to the canonical isoform?
The novel Drosha isoform is specifically expressed in embryonic stem cells and germ cells, differing from the canonical isoform.
What significance does the 5' UTR of the ESC/GC specific Drosha isoform hold?
The 5' UTR is different from the annotated isoform, which may influence its expression regulation.
Why is the study of cell-type specific isoforms of miRNA biogenesis factors important?
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What does the differential use of ATG codons suggest about the Drosha isoform in pluripotent cells?
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What did the reanalysis of Ribo-seq data reveal about Drosha in human iPSCs?
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What developmental role has not been previously reported for Drosha?
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What methodology was used to identify the novel TSS at the mouse Drosha locus?
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What implications might the presence of a specific Drosha isoform have on embryonic stem cell development?
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In what way does the novel Drosha isoform's start codon impact its protein translation?
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How might RNA binding proteins affect the expression of the ESC/GC specific Drosha isoform?
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What does the lack of documented internal transcription initiation of Drosha in human iPSCs suggest about species differences?
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What potential role does the identified novel TSS at the mouse Drosha locus play in ESCs and GCs?
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Why might the differential use of ATG codons in HEK293T cells and iPSCs be significant?
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How does the study of the novel Drosha isoform contribute to our understanding of miRNA regulation in mammals?
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What relevance does the identification of an isoform specifically expressed in germ cells have for reproductive biology?
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Study Notes
Novel Drosha Isoform in Embryonic Stem Cells
- MicroRNAs (miRNAs) are approximately 22 nucleotide small non-coding RNAs essential for regulating target mRNAs and play a critical role in normal development.
- Regulation of miRNA biogenesis factors like DGCR8, Dicer, and Ago2 is known to be influenced by cell-type specific isoforms, which is crucial for proper miRNA processing during mammalian development.
- A novel internal transcription start site (TSS) was identified at the mouse Drosha locus, leading to a specific isoform expressed predominantly in embryonic stem cells (ESC) and germ cells (GC).
Differences in Isoform Expression
- The 5' untranslated region (UTR) of the ESC/GC specific Drosha isoform differs from that of the canonical Drosha isoform.
- This variation in the 5' UTR may allow for distinct regulatory mechanisms, potentially involving upstream Open Reading Frames (uORFs) and RNA binding proteins that modulate isoform expression.
Mechanism of Translation
- The translation process for the ESC/GC specific Drosha isoform is expected to initiate at the second methionine codon of the canonical Drosha isoform, which may indicate a unique feature in pluripotent cells.
Comparative Analysis with Human Cells
- Analysis revealed no internal transcription initiation of Drosha in human induced pluripotent stem cells (iPSCs).
- Re-examination of Ribo-seq data suggested that HEK293T cells and iPSCs exhibit different usages of the initial ATG codons, with pluripotent cells favoring the second ATG. This implies a conserved mechanism of isoform expression across species, despite the differing approaches in mice and humans.
Novel Drosha Isoform in Embryonic Stem Cells
- MicroRNAs (miRNAs) are approximately 22 nucleotide small non-coding RNAs essential for regulating target mRNAs and play a critical role in normal development.
- Regulation of miRNA biogenesis factors like DGCR8, Dicer, and Ago2 is known to be influenced by cell-type specific isoforms, which is crucial for proper miRNA processing during mammalian development.
- A novel internal transcription start site (TSS) was identified at the mouse Drosha locus, leading to a specific isoform expressed predominantly in embryonic stem cells (ESC) and germ cells (GC).
Differences in Isoform Expression
- The 5' untranslated region (UTR) of the ESC/GC specific Drosha isoform differs from that of the canonical Drosha isoform.
- This variation in the 5' UTR may allow for distinct regulatory mechanisms, potentially involving upstream Open Reading Frames (uORFs) and RNA binding proteins that modulate isoform expression.
Mechanism of Translation
- The translation process for the ESC/GC specific Drosha isoform is expected to initiate at the second methionine codon of the canonical Drosha isoform, which may indicate a unique feature in pluripotent cells.
Comparative Analysis with Human Cells
- Analysis revealed no internal transcription initiation of Drosha in human induced pluripotent stem cells (iPSCs).
- Re-examination of Ribo-seq data suggested that HEK293T cells and iPSCs exhibit different usages of the initial ATG codons, with pluripotent cells favoring the second ATG. This implies a conserved mechanism of isoform expression across species, despite the differing approaches in mice and humans.
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Description
This quiz explores the role of a novel Drosha isoform specifically expressed in embryonic stem cells and germ line cells in mice. It highlights the significance of microRNAs in regulating target mRNAs and their impact on normal development.
