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RNA structure & Processing (Post-Transcription) Flashcards

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1
Q

What is the chemical structure of RNA?

A

Mostly single stranded but can base-pair with complementary sequence within itself.

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2
Q

What are coding RNAs?

A

Messenger RNAs (mRNA) that code for synthesis of proteins

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3
Q

Match the following non-coding RNAs to their definitions:

1) Ribosomal RNAs (rRNA)
2) Transfer RNAs (tRNA)
3) Small nuclear RNAs (snRNA)
4) Small nucleolar RNAs (snoRNA)
5) Micro RNAs (miRNA)
6) Short interfering RNAs (siRNA)
7) Piwi-interacting RNAs (piRNA)
8) Long non-coding RNAs (lncRNA)

A) Important in protein synthesis; adapter between mRNA and amino acids with a complex tertiary structure

B) Regulate gene expression by blocking translation of specific mRNAs (can also increase degradation)

C) Scaffolds for chromatin folding; X-chromosome inactivation and more. Controversial.

D) 1) primary component of the ribosome & 2) catalyze protein synthesis

E) Involved in pre-mRNA splicing (attach to proteins to form snRNPs - snRiboNucleoProtein /splicesome). There is various kinds; U1, U2, U4, U5, U6 snRNA

F) Processing and chemical modification of rRNAs (increase stability, half life and optimal function)

G) Regulate gene expression by blocking translation of specific mRNAs (can also increase degradation)

H) Bind to piwi proteins and protect the germ line from transposable elements.

A

Ribosomal RNAs (rRNA): 1) primary component of the ribosome & 2) catalyze protein synthesis

Transfer RNAs (tRNA): Important in protein synthesis; adapter between mRNA and amino acids with a complex tertiary structure

Small nuclear RNAs (snRNA): Involved in pre-mRNA splicing (attach to proteins to form snRNPs - snRiboNucleoProtein /splicesome). There is various kinds; U1, U2, U4, U5, U6 snRNA

Small nucleolar RNAs (snoRNA): Processing and chemical modification of rRNAs (increase stability, half life and optimal function)

Micro RNAs (miRNA): Regulate gene expression by blocking translation of specific mRNAs (can also increase degradation)

Short interfering RNAs (siRNA): Regulate gene expression by blocking translation of specific mRNAs (can also increase degradation)

Piwi-interacting RNAs (piRNA): Bind to piwi proteins and protect the germ line from transposable elements.

Long non-coding RNAs (lncRNA): Scaffolds for chromatin folding; X-chromosome inactivation and more. Controversial.

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4
Q

Which non-coding RNAs are important for regulating gene expression?

A

Micro RNAs (miRNA)
Short interfering RNAs (siRNA)

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5
Q

What does post-transcriptional gene control involve?

A

1) Processing of Eukaryotic Pre-mRNA
2) Regulation of Pre-mRNA processing
3) Transport of mRNA across the nuclear envelope
4) Processing of rRNA and tRNA

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6
Q

What is the difference between pre-mRNA and mRNA?

A

pre-mRNA: mRNA precursor containing introns and not cleaved at the poly(A) site

mRNA: fully processed mRNA with 5’cap, introns removed by RNA splicing and a poly(A)tail

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7
Q

Where do the properly processed mRNAs go from the nucleus? What happens to the improperly processed mRNA?

A

Properly processed mRNAs - exported to the cytoplasm so they can be translated by ribosome

Improperly processed mRNAs = blocked from export to the cytoplasm, degraded by the EXOSOME complex that has lots of ribonucleases. This complex can also modify the mRNA to make it functional.

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8
Q

Briefly describe the processing of eukaryotic pre-mRNA.

A

Pre-mRNA is capped, polyadenylated, spliced, and associated with RNPs (ribonucleoproteins) in the nucleus before export to the cytoplasm.

Splicing is done by a large ribonucleoprotein splicesome complex through two TRANSESTERIFICATION reactions.

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9
Q

A network of interactions between SR (serine-arginine rich) proteins, snRNPs, and splicing factors form a ______-____ recognition complex that specifies correct _____ sites.

A

Cross-exon

Splice

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10
Q

What are lariat RNAs?

A

The introns spliced out of the mRNA that are circular molecules with a short tail.

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11
Q

What is the G value paradox? How is it explained?

A

The number of protein-coding genes does not correlate with biological complexity.

It is in part due to differential processing of pre-mRNAs! (One protein coding gene can yield multiple protein isoforms?)

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12
Q

What are the different forms of alternative splicing? Briefly describe them.

A

1) Constitutive splicing: remove all introns, stitch all exons together

2) Exon skipping: an exon is skipped and still yields a functional protein

3) Intron retention: can have an intron retained as a “pseudo exon.” can be used to suppress protein activity.

4) Mutually exclusive exons: some exons never together; one or the other. Could be due to having different substrates of isoforms or having opposing catalytic activity.

5) Alternative 5’ splice site: what’s at the beginning of the mRNA is different

6) Alternative 3’ splice site: what’s at the end of the mRNA is different

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13
Q

Is the largest human gene the human gene with most exons?

A

No! The largest gene (Contactin-associated protein like 2 gene) has 24 exons spanning millions of base pairs, while the human gene with most exons (TTN gene) has 346 exons spanning 300,000 base pairs.

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14
Q

What is the difference between prokaryotic and eukaryotic mRNA?

A

Prokaryotic mRNA:
- no 5’ cap
- no polyA tail
- several genes of an operon transcribed into one mRNA
- one mRNA leads to multiple proteins

Eukaryotic mRNA:
- 5’ cap
- polyA tail
- one gene transcribed into one mRNA
- one mRNA leads to one protein (not considering alternative splicing)

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15
Q

What does RNA processing produce in eukaryotes?

A

RNA processing produces functional mRNA.

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16
Q

Where does RNA polymerase start transcription, where does it end?

A

RNA polymerase starts transcription at gene nucleotide +1, which is upstream (“before”) of the codon that encodes the first amino acid.

RNA polymerase stops transcription downstream (“after”) of the translation STOP codon.

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17
Q

What are the 5’ and 3’ untranslated regions (UTRs) of the mRNA?

A

These regions are transcribed into mRNA but will not be translated into proteins by the ribosome.

5’ UTR is recognized by the ribosome to bind and initiate translation.

3’ UTR is after the STOP codon.

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18
Q

Match the steps of RNA processing:

1) Step 1
2) Step 2
3) Step 3
4) Step 4

A) Endonuclease cleaves primary transcript (downstream of the STOP codon) at the poly(A) site

B) POLY(A) POLYMERASE adds 100-200 A residues

C) For short primary transcripts with few introns, splicing occurs after step 3.
For long primary transcripts with multiple introns, introns spliced out at the nascent RNA during transcription.

D) Nascent RNA 5’ end capped with 7-METHYLGUANYLATE during formation of the RNA transcript. Transcription terminated at one of multiple termination site downstream from the poly(A)site

A

Step 1: Nascent RNA 5’ end capped with 7-METHYLGUANYLATE during formation of the RNA transcript. Transcription terminated at one of multiple termination site downstream from the poly(A)site

Step 2: Endonuclease cleaves primary transcript (downstream of the STOP codon) at the poly(A) site

Step 3: POLY(A) POLYMERASE adds 100-200 A residues

Step 4: For short primary transcripts with few introns, splicing occurs after step 3.
For long primary transcripts with multiple introns, introns spliced out at the nascent RNA during transcription.

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19
Q

What is the function of the poly(A) tail?

A
  • Stabilizes the mRNAs in the nucleus and cytoplasm
  • Involved in mRNA translation
  • Protects mRNA from being degraded by exonucleases
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20
Q

What is the function of 5’ Methylated cap?

A
  • Protects mRNA from enzymatic degradation
  • Assists export of the mRNA to the cytoplasm
  • Bound by a protein factor required by ribosome to begin translation
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21
Q

(T/F) 5ʹ→5ʹ Linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and methyl group addition to the 2ʹ hydroxyl of the ribose of base 1 occur in all animal and most plant cells.

A

True!

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22
Q

(T/F) The methyl group can only be added to the 2ʹ hydroxyl of the ribose of base 1.

A

False! It can be added in base 2 as well.

Yeasts cells lack methyl group on base 1, but have it on base 2. While, vertebrate cells have methyl on both bases.

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23
Q

Match the steps of the synthesis of the 5’cap on eukaryotic mRNA:

1) Step 1
2) Step 2
3) Step 3
4) Step 4

A) GUANYLYL TRANSFERASE links GMP residue from GTP to the 5ʹ diphosphate of the transcript, creating a guanosine 5ʹ-5ʹ triphosphate structure.

B) 2’-O-METHYL TRANSFERASE – transfers methyl group from
S-adenosylmethionine to the 2ʹ oxygens of riboses of the first one or two RNA nucleotides (base 1/base 2)

C) PHOSPHOHYDROLASE removes the γ phosphate, while α and β phosphates remain associated with the cap

D) GUANYLYL-7-METHYL TRANSFERASE transfers methyl
group from S-adenosylmethionine to the guanine N7 position

A

Step 1: PHOSPHOHYDROLASE removes the γ phosphate, while α and β phosphates remain associated with the cap (all attached to the first base of pre-mRNA)

Step 2: GUANYLYL TRANSFERASE links GMP residue from GTP to the 5ʹ diphosphate of the transcript, creating a guanosine 5ʹ-5ʹ triphosphate structure.

Step 3: GUANYLYL-7-METHYL TRANSFERASE transfers methyl
group from S-adenosylmethionine to the guanine N7 position

Step 4: 2’-O-METHYL TRANSFERASE – transfers methyl group from
S-adenosylmethionine to the 2ʹ oxygens of riboses of the first one or two RNA nucleotides (base 1/base 2)

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24
Q

What is S-adenosylmethionine?

A

Methyl donor - gives methyl to the 5’ cap and to the 2ʹ hydroxyl of the ribose of base 1 or base 2 of the mRNA.

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25
Q

What is the RNA recognition motif (RRM)?

A

Most common RNA-binding domain in heterogeneous nuclear ribonuclearprotein proteins (hnRNP proteins) and other RNA-binding proteins.

It is composed of two α helices and four β strands. It has highly conserved RNP1 and RNP2 regions, which are located in the two central β strands.

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26
Q

What are the sex-lethal RNA recognition motif (RRM) domains?

A

Two RRM domains in Drosophila melanogaster Sex-lethal (Sxl)
protein.

The domains are oriented with the β sheets of the RRMs facing toward each other.

The domains, together, bind a nine-base sequence in transformer pre-mRNA to the surfaces of the positively charged β
sheets.

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27
Q

What are the intron splice site invariant bases (flanking bases found at frequencies higher than expected for a random distribution)?

A

5’ GU: splice donor
3’ AG: splice acceptor
Branch point adenosine

*Most conserved + important regions for splicing
*10/10 times, there is gonna GU at that 5’ site, there is gonna AG at that 3’ site and Adenosine in the branch point.
*This is what the two transesterification reactions involve

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28
Q

What is the polypyrimidine tract in the pre-mRNA?

What is the central region?

A

Polypyrimidine tract: found in most introns near the 3’ end

Central region: 40 bases-50kilo bases long. Not conserved, can be varied. Regulatory regions.

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29
Q

How many nucleotides at each end of an intron are necessary for splicing to occur at normal rates?

A

30-40 nucleotides

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30
Q

Match the following step of the two transesterification reactions that result in the splicing of exons in pre-mRNA:

1) Reaction 1
2) Reaction 2

A) 3’ Oxygen of EXON 1 binds to the 5’ Phosphate of EXON 2, breaking the ester bond between the phosphate of EXON 2 and the INTRON’s 3’ oxygen.

B) 5’ Phosphorus of the INTRON binds to 2’ Oxygen of BRANCH POINT A (ester bond) by breaking its bond with the 3’ Oxygen of EXON 1 (ester bond).

A

Reaction 1: 5’ Phosphorus of the INTRON binds to 2’ Oxygen of BRANCH POINT A (ester bond) by breaking its bond with the 3’ Oxygen of EXON 1 (ester bond).

Reaction 2: 3’ Oxygen of EXON 1 binds to the 5’ Phosphate of EXON 2, breaking the ester bond between the phosphate of EXON 2 and the INTRON’s 3’ oxygen.

The two exons are joined, the intron is released as a LARIAT stricture.

*look at slide 20 to fully understand

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31
Q

What are the key oxygens in the two two transesterification reactions that result in the splicing of exons in pre-mRNA?

A

1) 3’ oxygen of exon 1
2) 2’ oxygen of branch point A
3) 3’ oxygen of intron

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32
Q

snRNAs base pair with the pre-mRNA during splicing. Match the following snRNAs to what they base pair.

1) U1 snRNA
2) U2 snRNA

A) Base pairs with sequence surrounding the branch point A

B) Base pairs across 5’ splice site exon-intron junction

A

snRNAs base pair with the pre-mRNA.

U1 snRNA: base pairs across 5’ splice site exon-intron junction

U2 snRNA: base pairs with sequence surrounding the branch point A.

*U cause they are rich in uracil!

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33
Q

Why is branch point A not base paired but only its surroundings by U2 snRNA?

A

So that it can bulge out to allow the 2’ OH to participate in the first transesterification reaction.

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34
Q

What happens if there is a mutation in the pre-mRNA 5’ splice site and U1 snRNA can no longer base pair to it?

How is this restored?

A

Splicing is blocked!

U1 RNA has a compensating mutation, that restores the base pairing, that restores the splicing.

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35
Q

What is a spliceosome? What is it composed of?

A

A massive complex machinery that carries out splicing.

It is composed of over 200 proteins in eukaryotes and 5 snRNAs (U1, U2, U4, U5, U6).

36
Q

How much introns does each splicing event remove?

A

One intron is removed in each splicing event.

37
Q

Fill in the blanks:

All eukaryotic mRNAs have a 3’ poly (A) tail, except for ______ mRNAs.

3’ cleavage and polyadenylation of pre-mRNAs are _______ _______.

A

Histone!

Tightly coupled

38
Q

Match the following steps of cleavage and polyadenylation of pre-mRNAs in mammalian cells:

1) Step 1
2) Step 2
3) Step 3
4) Step 4

A) PAP (Poly(A) polymerase) stimulates cleavage at a poly(A) cleavage site (typically 15–30 nucleotides 3ʹ of the upstream poly(A) signal).

B) Cleavage factors are released; the downstream RNA cleavage product rapidly degraded. SLOW ADENYLATION: PAP adds 12 A residues (from ATP) at a slow rate to the 3’ hydroxyl group generated by cleavage reaction.

C) RAPID ADENYLATION: PABPN1 (Nuclear poly(A)-binding protein) binds to the initial short poly(A) tail and accelerates the rate of addition by PAP.

D) CPSF (Cleavage and polyadenylation specificity factor) binds to the upstream AAUAAA poly(A) signal. Then, CStF (Cleavage Stimulation Factor) interacts with a downstream GU- or U-rich sequence and with bound CPSF, forming a loop in the RNA. Lastly, CFI (cleavage factor I) and CFII bind to stabilize the complex.

A

Step 1: CPSF (Cleavage and polyadenylation specificity
factor) binds to the upstream AAUAAA poly(A) signal. Then, CStF (Cleavage Stimulation Factor) interacts with a downstream GU- or U-rich sequence and with bound CPSF, forming a loop in the RNA. Lastly, CFI (cleavage factor I) and CFII bind to stabilize the complex.

Step 2: PAP (Poly(A) polymerase) stimulates cleavage at a poly(A) cleavage site (typically 15–30 nucleotides 3ʹ of the upstream poly(A) signal)

Step 3: Cleavage factors are released; the downstream RNA cleavage product rapidly degraded. SLOW ADENYLATION: PAP adds 12 A residues (from ATP) at a slow rate to the 3’ hydroxyl group generated by cleavage reaction.

Step 4: RAPID ADENYLATION: PABPN1 (Nuclear poly(A)-binding protein) binds to the initial short poly(A) tail and accelerates the rate of addition by PAP.

39
Q

What signals PAP to stop adding As after 200-250 A residues have been added?

A

PABPN1 - Nuclear poly(A)-binding protein

40
Q

Match the following factors of cleavage and polyadenylation of pre-mRNAs in to the steps they are involved in:

1) Step 1
2) Step 2
3) Step 3
4) Step 4

A) PAP
B) PABN1
C) CPSF, CStF, CFI, CFII
D) PAP, cleavage factors removed

A

Step 1: CPSF (Cleavage and polyadenylation specificity
factor), CStF (Cleavage stimulation
factor), CFI, CFII

Step 2: PAP (Poly(A) polymerase)

Step 3: PAP, cleavage factors removed

Step 4: PABN1 (Nuclear poly(A)-binding protein)

41
Q

What does alternative polyadenylation lead to?

A

Different poly(A) structures.

Due to different regulations in polyadenylation -> poly(A) sites.

42
Q

What yields different mRNAs from the same gene?

A

1) Alternative promoters
2) Alternative splicing
3) Cleavage at different poly(A) sites (alternative polyadenylation)

43
Q

Which proteins regulate alternative splicing?

A

RNA-binding proteins that bind to specific sequences near splice sites

44
Q

(T/F) Rare RNA editing of mRNA sequences in the nucleus have important
consequences by altering the amino acid encoded by an edited codon.

A

True!

Octopus can edit their mRNA!

45
Q

SR (Serine-Argine-rich) proteins contribute to exon definition in ____ pre-mRNAs.

A

Long

46
Q

How many bases are exons usually composed of? How many bases are introns usually composed of?

A

Exon - 150 bases

Introns - 3500 bases, but longest exceed 500 kb

47
Q

What do SR proteins do?

A

They interact with EXONIC SEQUENCE ENHANCERS (ESE) within exons.

And they promote cooperative binding of U1 snRNP to a 5’ splice site and U2 snRNP to a branch point through a network of PROTEIN-PROTEIN interactions that span an exon!

48
Q

SR proteins bound to ESE promote cooperative binding of U1 snRNP to a 5’ splice site of the ________ intron.

Also promote U2 snRNP binding to a branch point of the _______ intron.

A

Downstream

Upstream

49
Q

(T/F) SR proteins do not interact with each other.

A

False! They interact with each other.

50
Q

What is the difference between Fibroblast fibronectin and Hepatocyte fibronectin?

A

Fibroblast fibronectin splice includes EIIA and EIIB exons that encode domains that bind to specific fibroblast membrane proteins.

Hepatocyte fibronectine splice out the EIIA and EIIB exons and their flaking introns. This leads them to not be able to bind to fibroblasts, but rather circulate in the bloodstream and form blood cots through fibrin-binding domains.

51
Q

How do individual hair cell neurons respond most strongly to a specific sound frequency?

A

By expressing a mixture of calcium activated potassium channel isoforms.

These isoforms are encoded by alternatively spliced mRNAs produced from the SAME primary transcript.

52
Q

(T/F) Alternative exons used at eight regions in the mRNA leads to 576 possible potassium channel isoforms, which respond to different frequencies by opening at different calcium concentrations.

A

True!

*8 possible splice sites

*Calcium concentration at which the channel opens determines the frequency of membrane potential oscillation - frequency to which the cell is tuned.

53
Q

What is the most extreme example of regulated alternative RNA processing yet discovered?

A

Drosophila Dscam gene!

It has the most number of isoforms!

54
Q

(T/F) Dscam isoform expression in Drosophila neurons helps to specify tens of millions of different specific synaptic
connections between neurons in the Drosophila brain.

A

True!

55
Q

(T/F) Out of the 38,016 possible peptides possible from the Drosophila Dscam gene, the ones we have studied so far are very important for branching of the species.

A

True!

56
Q

(T/F) Sex-lethal protein and the transformer protein are only expressed in female Dosrophilas because they induce a pre-mature stop codon in males.

A

True!

Pre-mature stop codon results in a dysfunctional protein.

57
Q

How are the sex lethal protein and the transformer protein related? Do both sexes express this protien?

A

Functional Sxl protein influences the splicing of the Tra gene.

It blocks exon 1-2 splicing in the tra gene, which would result in a premature stop codon.

Because females have the sex-lethal protein, their exon 1-2 splicing is blocked; Tra protein expressed

Males do not have the sex-lethal protein, their exon 1-2 splicing is not blocked. Due to exon 2 having a premature codon, this leads to a dysfunctional protein. Males DO NOT express this protein!

58
Q

How is tra protein related to Dsx protein? Do both sexes express this protein?

A

The Tra protein activates 3 and 4 exon splicing in the female Dsx protein.

Males lack functional Tra protein so exon 3 is bound to exon 5. But because there is no premature stop codon, it is functional.

Both sexes express the Dsx protein.

59
Q

(T/F) The female Dsx isoform activates genes with Dsx transcription factor binding sites, including genes that induce development of female characteristics, while the male Dsx isoform represses expression of the same target genes with Dsx binding sites.

A

True!

*go over the slides and the pics!

60
Q

Fill in the blanks:

The most common and extensively conserved type of alternatively spliced exons in the central nervous system (CNS) are called _______ because they are unusually short ___ to ____ bases long.

They are in multiples of _____ to maintain the _______ _______ of up- and downstream of exons of more typical longer lengths.

A

microexons; 3-27

three; reading frames

61
Q

How many patients with autism exhibit low levels of microexon splicing in the CNS?

A

1/3rd!

*low levels of microexon splicing: reading frame of other exons not maintained

62
Q

Where do the short stretches of amino acids encoded by microexons (1-9 amino acids) reside on? What are their functions?

A

They reside on PROTEIN SURFACES that participate in PROTEIN-PROTEIN interactions.

They are enriched in genes with critical functions in SYNAPTIC BIOLOGY.

63
Q

What is SRRM4? In which patients is it expressed in low levels? What does this tell us?

A

SRRM4 is a neuron-specific SR protein.

Patients with autism expressed low levels of the SRRM4 mRNA!

Frequency of micro-exon skipping correlated with degree in the reduction of SRRM4 levels! (low levels of SRRM4: low levels of microexon splicing)

64
Q

(T/F) Spinal Muscular Dystrophy is a neuromuscular disease that affects 1 in 10,000 people and is the result of a mutation in the survival of motor neuron 1 (SMA1).

A

True!

65
Q

What happens without a functional SMN (survival motor neuron) protein?

A

The motor neurons in the spinal cord and brain stem degenerate, resulting in MUSCLE WEAKNESS and ATROPHY.

66
Q

(T/F) A paralog of SMN1 in the human genome, SMN2, encodes an identical SMN protein. However, its pre-mRNA undergoes aberrant splicing, with 90% of mature SMN2 transcripts lacking exon 7 and producing a truncated, unstable polypeptide.

A

True!

SMN1 is the stable protein; very important 4 muscle and spinal formation

SMN2 is the unstable protein that gets degraded

67
Q

In an healthy individual, the SMN1 protein is ______, while the SMN2 protein i s________.

A

Active; inactive

68
Q

If the SMN1 gene has a mutation, where the expression of the healthy protein is disrupted and an unstable or inactive protein is made, what are the two possible treatment options?

A

1) Fix the mutation in SMN1
2) Change the splicing pattern of SMN2 to make it look like SMN1

69
Q

What is SPINRAZA (Nusinersen)? How does it work?

A

A treatment for spinal muscular dystrophy.

It is an antisense oligonucleotide that binds to intron 7 and prevents splicing repressors from binding, resulting in inclusion of exon 7 in SNM2.

Whereas normally it would have been spliced out. This results in a SMN1 like functional + stable protein!

70
Q

Do pre-mRNAs still bound to spliceosomes get exported?

A

No! This ensures only the mature mRNAs to reach the cytoplasm.

71
Q

What do mRNP exporters do?

A

Transport mRNPs (messenger ribonucleoprotein - mRNA bound with proteins) through the NUCLEAR PORE COMPLEX (NPC)

72
Q

Large NXF1 (nuclear export factor) subunit and a small NXT1 (nuclear export transporter) make a ________, that helps export mRNPs in and out of the nucleus.

A

HETERODIMER

*mRNP is the heterodimer composed of NXF1 with REF and NXT1.

73
Q

(T/F) NXF1 binds RNA and proteins in the mRNP complex with proteins including REF (RNA export factor), a component of the exon-junction complexes.

A

True!

74
Q

mRNP exporter associates with ___ proteins that are bound to exonic splicing enhancers.

A

SR

75
Q

While some mRNP proteins dissociate from nuclear mRNP complexes before export to the cytoplasm, which mRNPs remain associated?

A

CBC - Cap binding complex
NXF1/NXT1
PABPN1 (nuclear polyA-binding protein)

76
Q

What happens to the mRNP proteins that get exported with the mRNP?

A

They dissociate from the mRNP in the cytoplasm and are shuttled back into the nucleus through a Nuclear Pore Complex (NPC).

77
Q

For mRNP in cytoplasm:

The translation initiation factor ______ replaces the CBC (cap binding complex) bound to the 5’ cap.

_________ (cytoplasmic poly(A)-binding protein) replaces PAPBN1.

A

elF4E

PAPBC1

78
Q

(T/F) Stability of most mRNAs is controlled by poly(A) tail length and binding of various proteins to 5’ UTR sequences.

A

False!

Stability of most mRNAs is controlled by poly(A) tail length and binding of various proteins to 3’ UTR (untranslated region) sequences.

79
Q

Fill in the blanks:

mRNA translation can be regulated by ________ and RNA interference by
________ and various degradation, cytoplasmic splicing, and polyadenylation mechanisms.

A

Micro-RNAs

siRNAs

80
Q

Many mRNAs are transported to specific subcellular locations by sequence specific _____ ______ proteins that bind ___ UTR localization sequences

A

RNA binding

3’

81
Q

What are the three pathways for degradation of eukaryotic mRNAs?

A

1) Deadenylation-dependent mRNA decay
2) Deadenylation-independent mRNA decay
3) Endonuclease-mediated mRNA decay

They all degrade mRNA so it can’t get translated!

82
Q

What is the most common pathway for degradation of eukaryotic mRNAs?

A

Deadenylation-dependent mRNA decay

83
Q

How does Deadenylation-dependent mRNA decay work?

A

First, DEADENYLASE complex shortens poly(A) tail to ≤20 A residues.

This destabilizes the cytoplasmic poly(A)-binding proteins (PABPC1), which directly affects the 3’ end but also the 5’ end by weakening the interactions between the 5’cap and translation initiation factors.

This deadenylated mRNA can either:

1) be capped by the DCP1/DCP2 (decapping enzymes) deadneylation complex and degraded by XRN1(EXORIBONUCLEASE 1), a 5’ -> 3’ exonuclease

or

2) be degraded by 3’ -> 5’ exonucleases in cytoplasmic exosomes

84
Q

What are exosomes?

A

Multiprotein complex that degrade unprotected RNAs in the nucleus and cytoplasm.

85
Q

How does the deadenylation-independent mRNA decay pathway work?

A

mRNAs decapped before deadneylation and are degraded by XRN1 5’ –> 3’ exonuclease.

86
Q

How does the endonuclease-mediated mRNA decay pathway work?

A

mRNAs are cleaved INTERNALLY by an endonucleases, yielding in 2 unprotected ends, one without a 5’ cap and one without a poly(A) tail.

The mRNA fragment without the polyA tail gets degraded by a cytoplasmic exosome 3’ –> 5’

The mRNA fragment without the cap gets degraded by the XRN1 exonuclease 5’ –> 3’.

z Molecular Bio (9 decks)

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