Lecture 9: Post Transcriptional Regulation Flashcards
What are the two main functions of RNA interference?
• Repressing translation
• Degrading the mature mRNA
These functions help regulate gene expression and maintain cellular integrity.
What is the main type of RNA interference that base-pairs with the coding region?
Small interfering RNA (siRNA)
siRNA plays a crucial role in the silencing of specific mRNA transcripts.
What is the main type of RNA interference that base-pairs with the 3’ UTR?
microRNA (miRNA)
miRNA is involved in regulating gene expression by binding to mRNAs and preventing their translation.
What is the function of Piwi-interacting RNA (piRNA)?
Functional in the germline
piRNA is important for regulating gene expression in germ cells and protecting the genome from transposable elements.
What mechanism was discovered that involves exogenously provided dsRNA silencing an endogenous gene?
RNA interference (RNAi)
RNAi was first discovered in the organism C. elegans.
In what year was RNAi discovered?
1998
The discovery was significant for genetic research.
Who were the key researchers involved in the discovery of RNAi?
Craig Mello, Andrew Fire, Victor Ambros, Gary Ruvk
They were awarded the Nobel Prize in 2006 for their work.
What is the significance of the year 1993 in relation to miRNA?
The first miRNA was discovered
This discovery also took place in C. elegans.
What are the names of the first two miRNAs discovered?
Lin-4 and let-7
These miRNAs play crucial roles in the regulation of gene expression.
What is the length of the nts mentioned?
21-22 nts in length
What do these nts bind to?
Binds to the 3’UTR of an mRNA
What are the effects of binding to the 3’UTR?
Causes translational suppression or mRNA degradation
What diseases are these nts implicated in?
Implicated in many diseases including neurodegenerative diseases and cancer
Where are these nts found?
Found intracellularly and extracellularly
What roles do these nts serve?
Serve as therapeutic targets and diagnostic biomarkers
What do ribosomes do?
Ribosomes translate mature mRNAs into proteins, the building blocks for life.
What are ASOs?
ASOs are small single-stranded RNA molecules that have exact complementarity to a target mRNA. Once bound, they induce post-transcriptional gene silencing by preventing translation of the mRNA.
What are siRNAs?
siRNAs are small double-stranded RNA molecules that have exact complementarity to a target mRNA. Once associated with the RISC complex, it binds to its target mRNA and induces gene silencing by preventing translation of the mRNA.
What are miRNA mimics?
Small double-stranded RNA molecules that guide the RISC complex to its target mRNA, leading to gene silencing.
How do miRNA mimics function?
They bind with imperfect complementarity to target mRNA, blocking translation or causing mRNA degradation.
What are miRNA inhibitors?
Small single-stranded RNAs that bind to and suppress their target miRNA, restoring mRNA translation.
What are aptamers?
RNA, DNA, or RNA/DNA hybrids that form tertiary structures and bind to a target molecule.
What is the function of aptamers?
They can suppress or enhance the pathway of the target molecule.
What drug was approved by the FDA on 23 December 2016 for spinal muscular atrophy?
Nusinersen (Spinraza)
This drug is an antisense oligonucleotide (ASO) used to treat SMA.
What is spinal muscular atrophy (SMA)?
A fatal genetic disease that affects children and adults
SMA is a neuromuscular disease affecting 1 in 10,000 people.
What causes spinal muscular atrophy?
Mutations in the gene survival of motor neuron 1 (SMN1)
These mutations lead to a lack of functional SMN protein.
What happens to motor neurons in individuals with spinal muscular atrophy?
They degenerate, resulting in muscle weakness and atrophy
This degeneration occurs due to the absence of functional SMN protein.
What percentage of infants born with SMA show symptoms before six months of age?
60%
Early onset is a significant aspect of the disease.
What is the typical prognosis for infants born with SMA?
Less than two years
This highlights the severity of the disease if untreated.
What gene is associated with spinal muscular atrophy?
survival of motor neuron 1 (SMN1)
SMN1 mutations lead to spinal muscular atrophy.
What is the paralog of SMN1 in the human genome?
SMN2
SMN2 encodes an identical SMN protein but with significant differences in splicing.
How does the pre-mRNA of SMN2 differ from that of SMN1?
SMN2 pre-mRNA undergoes aberrant splicing, with 90% of transcripts lacking exon 7
This results in a truncated and unstable polypeptide.
Who elucidated the molecular basis of SMN2 exon 7 skipping?
Ravendra Singh and Adrian Krainer
Their research was conducted in the late 1990s to early 2000s.
What type of therapy involves ASO repressing splicing suppressors?
Antisense oligonucleotide (ASO) therapy
This approach aims to modify splicing patterns.
How quickly did the FDA approve nusinersen after the NDA was filed?
Three months
Nusinersen is a treatment for spinal muscular atrophy.
What is the primary focus of RNA Pharmaceuticals?
Development and application of RNA-based therapies
RNA Pharmaceuticals include mRNA vaccines and RNA interference (RNAi) therapies.
What type of medical products do vaccines represent?
Preventive health measures designed to induce immunity
Vaccines work by stimulating the body’s immune response to recognize and combat pathogens.
What virus is associated with the disease COVID-19?
SARS-CoV-2
SARS-CoV-2 is a novel coronavirus first identified in December 2019.
