MicroRNA Regulation and Functions

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Questions and Answers

What role does mismatched miRNA play in gene regulation?

It reduces the strength of the miRNA-mRNA interaction.

It guarantees precise targeting of a specific mRNA.

It can accommodate more targets to downregulate multiple genes. (correct)

It enhances the effectiveness of siRNA against viral infections.

Where does the 'seed' region of miRNA typically match with target mRNA?

5' UTR region

3' UTR region (correct)

Exon region

Coding region

What is the function of miR-1 in muscle development?

It inhibits transcription factors involved in muscle growth.

It regulates the expression of miR-133 only.

It is essential for heart rhythm stabilization.

Its deletion causes lethality and heart defects in mice. (correct)

Which proteins and factors are involved in skeletal muscle growth and regeneration?

Transcription factors and growth signals Signup and view all the answers

What changes in miRNA levels indicate after a heart attack?

They correlate with the extent of damage and repair processes. Signup and view all the answers

What is a potential outcome of FXR1's association with the large ribosomal subunit?

Enhanced translation efficiency Signup and view all the answers

Which of the following accurately describes circRNAs?

They have a stable circular structure. Signup and view all the answers

What role do miRNA sponges such as circRNAs play in gene regulation?

They provide additional miRNA binding sites. Signup and view all the answers

What is the role of Dicer in miRNA biogenesis?

It processes pre-miRNA into mature miRNA. Signup and view all the answers

How does the expression of a single siRNA affect circRNA levels?

It leads to circRNA degradation. Signup and view all the answers

What largely determines the strength of miRNA and mRNA interaction?

The sequence match in the seed region Signup and view all the answers

Which of the following best describes a role of mismatched miRNA?

It allows control of multiple gene targets simultaneously. Signup and view all the answers

Which miRNA is specifically required for proper muscle development in mice?

miR-1-1 Signup and view all the answers

What is a potential clinical application of monitoring miRNA levels in blood after a heart attack?

To evaluate the extent of cardiac damage and repair Signup and view all the answers

How do miRNAs interact with their target mRNAs to regulate gene expression?

By forming stable complexes that prevent translation Signup and view all the answers

What is the role of FXR1 in translation regulation?

It enhances ribosome recruitment to the large ribosomal subunit. Signup and view all the answers

How do circRNAs function as miRNA sponges?

They provide binding sites that inhibit miRNA activity on target mRNAs. Signup and view all the answers

What is a key characteristic of circRNAs compared to linear RNAs?

CircRNAs have no 5’ or 3’ ends, making them more stable. Signup and view all the answers

What does the reporter system involving dual fluorophores measure?

The ratio of miRNA-induced gene regulation. Signup and view all the answers

How are miRNAs produced from their precursor form?

By maturation through the Dicer enzyme. Signup and view all the answers

Study Notes

BMSC 320 Nucleic Acids: From Central Dogma to Human Disease

Nucleic acids play a crucial role in human disease, acting as a bridge from central dogma to human disease.
Gene silencing involves precursor RNA, dicer, and miRNA leading to mRNA degradation.
RNA interference (RNAi) uses duplex RNA, dicer, and siRNA for gene silencing.
Translation inhibition and mRNA degradation are key mechanisms in gene silencing.
Mismatched miRNA can target more genes, acting as a regulatory mechanism.
Fully complementary siRNAs mimic some viral infections that use dsRNA, so degradation evolved as a defense mechanism
Mismatched miRNA can accommodate many more targets and be used as an additional control mechanism to downregulate translation of multiple genes simultaneously

miRNA in Muscle Development

miR-1 is essential for muscle development.
Deletion of miR-1-1 in mice leads to lethal heart defects.
Several miRNA orthologs are involved in muscle development, including miR-27, miR-133, Pax3, Pax7, SRF, IGF-1, PTEN, histone deacetylases, and myomaker protein.

miRNA in Tissue Damage & Repair

miR-1 and miR-133 regulate heart growth, differentiation, and rhythm.
miRNA levels in blood show significant changes after heart attacks, implying potential diagnostic applications.
Altered miRNA expression after heart attacks can indicate the extent of damage and repair processes.
Research is studying miRNA levels as potential diagnostic tools for various conditions, including infections, liver disease, cancers, and endometriosis.
miRNA can possibly be used to diagnose and treat cardiac infections.

Up-miRNAs?

Multiple models/organisms indicate miRNAs can also enhance translation.
FXR1 is an RNA binding protein associated with the large ribosomal subunit, upregulating translation likely due to ribosome recruitment.
The mechanisms by which miRNAs upregulate translation remain an area of active research
Up-regulation of translation is a process involving efficient ribosome recruitment.

The Power of a Good Reporter System

Eukaryotic plasmid transformed into mammalian cells expresses dual fluorophores.
The ratio of blue/red fluorescence is measured after miRNA treatment.
ST6GAL1 3' UTR shows regulation by only 4% of the miRNA library, but effector miRNAs are upregulating by a factor of 3x more.
The system ensures both fluorescent genes are in the same cell for accurate measurement.

Another Regulator: circRNAs

circRNAs are covalently closed RNA circles produced during splicing.
They are typically stable due to lack of ends and resistant to exonuclease degradation.
They can degrade by endonucleolytic mechanisms, such as DNA-pairing and RNAse H-mediated cleavage.
circRNAs are often not translatable, but some are functionally relevant.
Some circRNAs contain genes that backsplice often, thus preventing this regulate other events.
CircRNA biogenesis can occur through direct back-splicing, intron pairing, and exon skipping

miRNA Sponges: circRNAs

Many detected circRNAs have multiple miRNA binding sites.
They can act as competitive inhibitors, limiting miRNA target regulation.
Expression of a single siRNA can lead to circRNA degradation, releasing a miRNA payload.
Long non-coding RNAs (lncRNAs) can also act as miRNA sponges.

Summary

miRNA and siRNA originate from dsRNA intermediates.
siRNAs are often from viral infections while miRNAs originate from their own genes or mirtrons.
Pri-miRNA converts to pre-miRNA via microprocessor complexes and is exported.
miRNA is loaded into RISC to target mRNA, leading to its degradation or silencing.
This silencing may occur on a full- or partial-match basis.

Integrating Control RNAs into Gene Expression

DNA methylation and chromatin regulators influence gene expression, potentially impacting downstream processes like transcription and translation.
miRNA and circRNA influence the translation process for mRNA to protein.
Many gene products can be regulated by similar regulators in a defined sequence.
Chromatin regulators, DNA methylation, transcriptional activators, transcriptional repressors, splicing factors, and siRNAs, IncRNAs, and circRNAs each play a role in gene expression regulation.

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Description

Explore the complex roles of miRNAs in gene regulation, muscle development, and responses to cellular stress. This quiz covers key concepts like the seed region, miRNA sponges, and factors involved in skeletal muscle growth. Test your knowledge on how miRNAs influence biological processes and the implications in health and disease.