Post-transcriptional eukaryotic gene regulation

Question 1

What is the relationship between mRNA transcript abundance and protein abundance in the cell?

Answer 1

Weak non linear relationship

Question 2

What does the relationship between mRNA and protein abundance mean we cannot predict?

Answer 2

Cannot predict protein abundance based off of abundance of mRNAs that are transcribed.

Question 3

percentage ability to predict protein abundnace with given mRNA abundance

Answer 3

13% (can barely predict it)

Question 4

Why is there sometimes high mRNA transcript abundance but low protein abundance?

Answer 4

mRNA is blocked by miRNAs so the ribosome cannot translate it to protein.

Question 5

What are micro RNAs?

Answer 5

small non-coding RNAs that bind mRNA triggering degradation or altering affinity for ribosome

Question 6

What was the first miRNA gene to be discovered?

Answer 6

lin-4

Question 7

How many miRNA genes in the human genome?

Answer 7

2600

Question 8

What do miRNAs bind to?

Answer 8

bind to specific sequence on target mRNA

Question 9

What does perfect complementary binding of miRNA and target mRNA cause?

Answer 9

Endonucleases see target mRNA as double strand mRNA and therefore cleave it which in turn causes degradation of the mRNA.

Question 10

What does imperfect complementary binding of miRNA and target mRNA cause?

Answer 10

Translational inhibition
(Target mRNA isn't cleaved however miRNA prevents ribosome from moving along the gene)

Question 11

Why did miRNAs evolve?

Answer 11

To provide innate immunity against viruses and retro-transposons

Question 12

How many human miRNAs are there which target human viruses?

Answer 12

2000 human miRNAs that target 400 different human viruses

Question 13

Relationship between mild COVID symptoms and miRNAs.

Answer 13

People with more miRNA genes being expressed in lung epithelial cells produce more miRNAs which would degrade COVID mRNA. They have both adaptive immune response and also miRNAs to provide immunity.

Question 14

What is let-7?

Answer 14

a retro-transposon

Question 15

How many human miRNAs are predicted to target COVID-19?

Answer 15

120

Question 16

What are RNA binding proteins?

Answer 16

Proteins that bind to mRNA changing stability and affinity for the ribosome

Question 17

How many genes in the human genome encode RNA binding proteins?

Answer 17

1500 genes

Question 18

Role of RNA binding proteins

Answer 18

upregulate or downregulate gene expression

Question 19

What is codon usage bias?

Answer 19

Where codons that code for the same amino acid are used at higher frequencies than others.

NOTE: If the codon that is used has a tRNA associated with it that are in higher abundance than those associated with another codon (that codes for the same amino acid) then over any given period of time more protein will be translated because there are more tRNAs bringing in the amino acid.

Question 20

When will mRNA produce a larger abundance of protein? 9in terms of codons)

Answer 20

when the codon on the mRNA has highly abundant tRNAs (with the correct anticodon). So in any given amount of time more tRNAs will stop off and deposit their amino acid at that codon so teh polypeptide elongates faster.

Question 21

What are synonymous codons?

Answer 21

Different codons that encode the same amino acid

Question 22

What allows one tRNA to bind multiple different codons?

Answer 22

deamination of adenine to inosine

Question 23

What is the main reason why mRNA abundance is a poor predictor of protein abundance?

Answer 23

Due to codon usage bias, mRNAs that have more translationally optimal codons (because they are associated with tRNAs which have a higher frequency in the cell) produce more proteins per mRNA transcript.

So there could be high mRNA abundance but the mRNA contains codons which are associated with lower frequency tRNAs so in a period of time less protein is produced.

Question 24

How did codagenix create an attenuated vaccine for covid-19?

Answer 24

Replaced translationally optimal codons with translationally bad codons so that the same viral particle is produced but it relicates much more poorly (slowly?).