Lecture 9: Post Transcriptional Regulation

Question 1

What are the two main functions of RNA interference?

Answer 1

• Repressing translation
• Degrading the mature mRNA

These functions help regulate gene expression and maintain cellular integrity.

Question 2

What is the main type of RNA interference that base-pairs with the coding region?

Answer 2

Small interfering RNA (siRNA)

siRNA plays a crucial role in the silencing of specific mRNA transcripts.

Question 3

What is the main type of RNA interference that base-pairs with the 3’ UTR?

Answer 3

microRNA (miRNA)

miRNA is involved in regulating gene expression by binding to mRNAs and preventing their translation.

Question 4

What is the function of Piwi-interacting RNA (piRNA)?

Answer 4

Functional in the germline

piRNA is important for regulating gene expression in germ cells and protecting the genome from transposable elements.

Question 5

What mechanism was discovered that involves exogenously provided dsRNA silencing an endogenous gene?

Answer 5

RNA interference (RNAi)

RNAi was first discovered in the organism C. elegans.

Question 6

In what year was RNAi discovered?

Answer 6

1998

The discovery was significant for genetic research.

Question 7

Who were the key researchers involved in the discovery of RNAi?

Answer 7

Craig Mello, Andrew Fire, Victor Ambros, Gary Ruvk

They were awarded the Nobel Prize in 2006 for their work.

Question 8

What is the significance of the year 1993 in relation to miRNA?

Answer 8

The first miRNA was discovered

This discovery also took place in C. elegans.

Question 9

What are the names of the first two miRNAs discovered?

Answer 9

Lin-4 and let-7

These miRNAs play crucial roles in the regulation of gene expression.

Question 10

What is the length of the nts mentioned?

Answer 10

21-22 nts in length

Question 11

What do these nts bind to?

Answer 11

Binds to the 3’UTR of an mRNA

Question 12

What are the effects of binding to the 3’UTR?

Answer 12

Causes translational suppression or mRNA degradation

Question 13

What diseases are these nts implicated in?

Answer 13

Implicated in many diseases including neurodegenerative diseases and cancer

Question 14

Where are these nts found?

Answer 14

Found intracellularly and extracellularly

Question 15

What roles do these nts serve?

Answer 15

Serve as therapeutic targets and diagnostic biomarkers

Question 16

What do ribosomes do?

Answer 16

Ribosomes translate mature mRNAs into proteins, the building blocks for life.

Question 17

What are ASOs?

Answer 17

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.

Question 18

What are siRNAs?

Answer 18

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.

Question 19

What are miRNA mimics?

Answer 19

Small double-stranded RNA molecules that guide the RISC complex to its target mRNA, leading to gene silencing.

Question 20

How do miRNA mimics function?

Answer 20

They bind with imperfect complementarity to target mRNA, blocking translation or causing mRNA degradation.

Question 21

What are miRNA inhibitors?

Answer 21

Small single-stranded RNAs that bind to and suppress their target miRNA, restoring mRNA translation.

Question 22

What are aptamers?

Answer 22

RNA, DNA, or RNA/DNA hybrids that form tertiary structures and bind to a target molecule.

Question 23

What is the function of aptamers?

Answer 23

They can suppress or enhance the pathway of the target molecule.

Question 24

What drug was approved by the FDA on 23 December 2016 for spinal muscular atrophy?

Answer 24

Nusinersen (Spinraza)

This drug is an antisense oligonucleotide (ASO) used to treat SMA.

Question 25

What is spinal muscular atrophy (SMA)?

Answer 25

A fatal genetic disease that affects children and adults ## Footnote SMA is a neuromuscular disease affecting 1 in 10,000 people.

Question 26

What causes spinal muscular atrophy?

Answer 26

Mutations in the gene survival of motor neuron 1 (SMN1) ## Footnote These mutations lead to a lack of functional SMN protein.

Question 27

What happens to motor neurons in individuals with spinal muscular atrophy?

Answer 27

They degenerate, resulting in muscle weakness and atrophy ## Footnote This degeneration occurs due to the absence of functional SMN protein.

Question 28

What percentage of infants born with SMA show symptoms before six months of age?

Answer 28

60% ## Footnote Early onset is a significant aspect of the disease.

Question 29

What is the typical prognosis for infants born with SMA?

Answer 29

Less than two years ## Footnote This highlights the severity of the disease if untreated.

Question 30

What gene is associated with spinal muscular atrophy?

Answer 30

survival of motor neuron 1 (SMN1) ## Footnote SMN1 mutations lead to spinal muscular atrophy.

Question 31

What is the paralog of SMN1 in the human genome?

Answer 31

SMN2 ## Footnote SMN2 encodes an identical SMN protein but with significant differences in splicing.

Question 32

How does the pre-mRNA of SMN2 differ from that of SMN1?

Answer 32

SMN2 pre-mRNA undergoes aberrant splicing, with 90% of transcripts lacking exon 7 ## Footnote This results in a truncated and unstable polypeptide.

Question 33

Who elucidated the molecular basis of SMN2 exon 7 skipping?

Answer 33

Ravendra Singh and Adrian Krainer ## Footnote Their research was conducted in the late 1990s to early 2000s.

Question 34

What type of therapy involves ASO repressing splicing suppressors?

Answer 34

Antisense oligonucleotide (ASO) therapy ## Footnote This approach aims to modify splicing patterns.

Question 35

How quickly did the FDA approve nusinersen after the NDA was filed?

Answer 35

Three months ## Footnote Nusinersen is a treatment for spinal muscular atrophy.

Question 36

What is the primary focus of RNA Pharmaceuticals?

Answer 36

Development and application of RNA-based therapies ## Footnote RNA Pharmaceuticals include mRNA vaccines and RNA interference (RNAi) therapies.

Question 37

What type of medical products do vaccines represent?

Answer 37

Preventive health measures designed to induce immunity ## Footnote Vaccines work by stimulating the body's immune response to recognize and combat pathogens.

Question 38

What virus is associated with the disease COVID-19?

Answer 38

SARS-CoV-2 ## Footnote SARS-CoV-2 is a novel coronavirus first identified in December 2019.