Podcast
Questions and Answers
How do foreign RNA molecules contribute to the functional sequestering of microRNAs?
How do foreign RNA molecules contribute to the functional sequestering of microRNAs?
- They increase the expression of genes and networks controlled by functional microRNAs.
- They 'sponge' away functional microRNAs, leading to de-repression of genes and networks normally controlled by these microRNAs. (correct)
- They directly degrade functional microRNAs, preventing them from binding to their target mRNAs.
- They alter the structure of functional microRNAs, causing them to bind to different mRNA targets.
What is the functional consequence of a sponge RNA having a higher mRNA:miRNA ratio compared to coding mRNAs?
What is the functional consequence of a sponge RNA having a higher mRNA:miRNA ratio compared to coding mRNAs?
- It allows the sponge RNA to more effectively compete for and sequester available microRNAs. (correct)
- There is no functional consequence.
- It causes global downregulation of all mRNA transcripts within the cell.
- It results in the enhanced degradation of the sponge RNA but not the coding mRNAs.
Circular RNAs (circRNAs) are formed via:
Circular RNAs (circRNAs) are formed via:
- Non-canonical mRNA splicing reactions that covalently close exonic transcripts. (correct)
- Canonical mRNA splicing reactions that join the 5' and 3' ends of exonic transcripts.
- Reverse transcription of linear RNA followed by self-ligation.
- Cleavage of linear RNA into smaller fragments, followed by circularization.
Where are circRNAs most abundantly expressed?
Where are circRNAs most abundantly expressed?
What is the potential function of circRNAs?
What is the potential function of circRNAs?
A circRNA known as CDR1as, discovered by the Kjems laboratory, is notable for which characteristic?
A circRNA known as CDR1as, discovered by the Kjems laboratory, is notable for which characteristic?
What processes are CDR1as and its interactions with miRNAs important for?
What processes are CDR1as and its interactions with miRNAs important for?
What was the main approach used by Piwecka et al. (2017) to investigate the function of CDR1as?
What was the main approach used by Piwecka et al. (2017) to investigate the function of CDR1as?
Within which cell types in the mouse brain is Cdr1as highly expressed?
Within which cell types in the mouse brain is Cdr1as highly expressed?
What were the electrophysiological findings in the Cdr1as knockout mouse model?
What were the electrophysiological findings in the Cdr1as knockout mouse model?
How are miR-7 and miR-671 affected in Cdr1as knockout brains?
How are miR-7 and miR-671 affected in Cdr1as knockout brains?
What effect does the loss of Cdr1as have on the expression of immediate early genes like Fos?
What effect does the loss of Cdr1as have on the expression of immediate early genes like Fos?
How does CDR1as influence miR-7?
How does CDR1as influence miR-7?
In relation to microRNAs, what role does the packaging play within cells?
In relation to microRNAs, what role does the packaging play within cells?
What is one conclusion from analyzing circulating exosomal microRNAs?
What is one conclusion from analyzing circulating exosomal microRNAs?
What is the purpose of Dicer in context of this lecture?
What is the purpose of Dicer in context of this lecture?
What is one observation when Dicer is lacking?
What is one observation when Dicer is lacking?
What is an important source of exosomal miRNAs?
What is an important source of exosomal miRNAs?
What can adipose-derived circulating miRNAs affect?
What can adipose-derived circulating miRNAs affect?
What is the role of adipose tissue in the regulation of metabolism?
What is the role of adipose tissue in the regulation of metabolism?
In the study of ADicerKO mice, what was observed regarding the levels of circulating exosomal miRNAs?
In the study of ADicerKO mice, what was observed regarding the levels of circulating exosomal miRNAs?
What effect did the transplantation of white and brown adipose tissue have on ADicerKO mice?
What effect did the transplantation of white and brown adipose tissue have on ADicerKO mice?
What has been shown from the exosomal transfer via adipose tissue?
What has been shown from the exosomal transfer via adipose tissue?
Adipose tissue is an important source of circulating ______.
Adipose tissue is an important source of circulating ______.
DicerKO in mice has a defect in miRNA processing in what tissue type?
DicerKO in mice has a defect in miRNA processing in what tissue type?
How adipocyte levels could change in diseases with altered fat mass?
How adipocyte levels could change in diseases with altered fat mass?
Adipose-derived circulating miRNAs can have what type of effects?
Adipose-derived circulating miRNAs can have what type of effects?
What new type of communication do adipose depots exhibit?
What new type of communication do adipose depots exhibit?
Flashcards
Functional sequestering of microRNAs
Functional sequestering of microRNAs
Highly expressed cellular or foreign RNA molecules that can functionally sequester or 'sponge' away functional microRNAs, causing de-repression of genes and networks.
CircRNAs
CircRNAs
RNAs produced by regular transcription from genomic DNA, but the two ends of the (usually) exonic transcripts are covalently closed.
CDR1as
CDR1as
A circRNA discovered to have >70 binding sites for miR-7 and also has a number of binding sites for miR-671.
Functions of CDR1as
Functions of CDR1as
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Effect of CDR1as on miRNAs
Effect of CDR1as on miRNAs
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RNA transport
RNA transport
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DicerKO mice
DicerKO mice
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Adipose-derived miRNAs
Adipose-derived miRNAs
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Study Notes
CircRNAs as RNA Sponges
- CircRNAs relate to the sponging effect of other RNAs like viral RNAs
- CircRNAs are covalently closed, usually from exonic transcripts
- This occurs via non-canonical mRNA splicing from genomic DNA.
- CircRNAs tend to be weakly expressed except in animal brains, like the mouse brain
- In mouse brains, a few hundred circRNAs are highly expressed, with developmentally specific expression patterns
CDR1as as a miRNA Sponge
- The Kjems laboratory discovered CDR1as has over 70 binding sites for miR-7
- CDR1as also has a number of binding sites for miR-671
- CDR1as and its direct interactions with miRNAs are important for sensorimotor gating and synaptic transmission
- CircRNAs biological functions are important in the mammalian brain
Piwecka et al. Study of CDR1as
- Piwecka et al. knocked out circRNA to determine if CDR1as functionally sequesters miRNAs
- CDR1as has over 70 miR-7 binding sites, giving it the potential to sequester this miRNA
- RNA fluorescence in situ hybridization (FISH) was performed to determine Cdr1as expression patterns in the mouse brain
- Co-staining with neural markers revealed that Cdr1as was highly expressed in neurons, specifically excitatory neurons
- Cdr1as expression wasn't present in glial cells such as oligodendrocytes and astrocytes
- Using CRISPR-Cas9, the Cdr1as locus was deleted
- RNA in situ hybridization confirmed successful genetic ablation of Cdr1as
CDR1as Impact on miRNA Function
- CDR1as regulates two microRNAs, miR-7 and miR-671
- Binding to CDR1as decreased and increased microRNA function, leading to dysfunction of excitatory synaptic transmission
- Neuronal CDR1as stabilizes or transports miR-7, but despite having over 70 binding sites, it's not an inhibitor of miR-7 function
- MiR-671 target levels increase, suggesting that CDR1as acts like a sponge for this miRNA
- Mechanistically, CDR1as regulates miR-7 stability or transport, while regulating miR-671 levels through sequestering
- Functionally, CDR1as, with miRNAs are important for sensorimotor gating and synaptic transmission
miRNAs as Signals and the Role of Exosomes
- miRNAs can serve to facilitate cell-cell signaling similar to proteins like growth factors
- Blood and skin contain high levels of nuclease enzymes that destroy foreign RNA and DNA
- RNA must be packaged and protected to travel between cells
- miRNAs can be transported via exosomes
miRNAs in Adipocytes
- Mice were generated lacking Dicer in adipose tissue to understand the role of miRNAs in fat
- DicerKO mice had a defect in miRNA processing in adipose tissue
- This resulted in decreased white adipose tissue (WAT), whitening of brown adipose tissue (BAT), insulin resistance, and altered circulating lipids
- Adipose tissue is an important source of circulating exosomal miRNAs
- Different adipose depots contribute different exosomal miRNAs to the circulation
- Adipose-derived circulating miRNAs have systemic effects, by regulating mRNA expression and translation.
- Levels of miRNAs could change in diseases like lipodystrophy/obesity, diabetes, and aging
- A new mechanism of cell–cell crosstalk is provided
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