Translation Regulation Flashcards
(28 cards)
How many steps are there in regulation of gene expression in eukaryotes?
There are at least 6 main mechanism involved in the regulation of gene expression in eukaryotes
What is RNA Processing?
Differential splicing of primary transcripts can lead to the production of mRNAs which encode for completely different proteins
-7-methylguanosine cap added to 5’ end and poly A tail added to 3’ end
Primary transcript, hnRNA= (heteronuclear RNA also known as primary RNA)
What is differential splicing?
Differential splicing yields alternate mRNA transcripts
What influences differential splicing?
Proteins expressed differently in different cells can influence splicing
What happens to mRNA during translation initiation?
Circulization
Describe global mechanisms of translation regulation
Global
-affects most mRNAs
-Due to rate limiting activities of translation initiation factors
Describe specific mechanisms of translation regulation
Affects particular mRNAs
Different mechanisms
Response to
- Nutrients
- Development cues
- Cell polarity/location
What are the types of mechanisms of translational regulation?
Global and specific
Elements within the mRNA and modifications of the molecule are…
Involved in regulating translation
What happens when mRNAs are uncapped?
Efficient translation requires presence of a complete 7-methyl-guanosine “cap” at the 5’ end of mRNA
Ex. Tobacco hornworm with:
Unfertilized oocyte:
5’ guanosine on oocyte mRNAs are not methylated therefore they can’t attach to ribosomes
After fertilization:
7-methyl added to 5’ guanosine on mRNAs-association with ribosome
Describe differential mRNA polyadenylation for mRNAs encoding for oocyte growth
During oogenesis: mRNAs with long poly-A tails leads to immediate translation
After oocyte maturation/fertilization: poly-A tails are removed leads to translation stops
Describe differential mRNA polyadenylation for mRNAs encoding proteins needed for: cleavage
During oogenesis: mRNAs have most of their poly-A clipped off (15-90 A’s retained) leads to blocked translation
After oocyte maturation/ fertilization: Stored maternal mRNAs acquire long poly-A tails (150-600 A’s)-translation begins
What marks mRNAs to be selectively polyadenylated at fertilization?
Specific nucleotide sequence (cytoplasmic polyadenylation element; CPE) in the 3’ trailer (3 UTR) of the message marks the mRNAs to be selectively polyadenylated at fertilization (UUUAU)
Explain the functioning of interfering proteins
Ex1. Interfering proteins: Maskin proteins prevent mRNA polyadenylation and translation
- Stored mRNAs in early embryos contain short poly-A tails
- CPE Binding protein (CPEB) recruits Maskin.
- Progesterone (production resulting from fertilization) activates protein kinases that phosohorylates CPEB
- Maskin is released
- mRNA is poly-adenylated
- PABP binding initiates translation
Describe the PUF family of proteins
-pumilo proteins in drosophila
PUF proteins bind to element in the 3’ UTR of the mRNA and prevent polyadenylation of the mRNA
They may also inhibit translation of the mRNA by interacting with the 5’ UTR or 7mG cap
Describe interacting proteins “masked messages”
Unfertilized egg-mRNAs are packaged in ribonucleoprotein (RNP) particles —> no translation of mRNAs- mRNAs can’t attach to ribosomes due to RNPs
At fertilization- ionic changes ( increase in calcium ions, sodium ions, pH) increase ca7se release of “masking proteins”—> Translation of mRNA- mRNAs are free to attach to ribosome
What are the functions of internal Ribosomal entry sites (IRES) ?
allow for cap independent translation
Viral mRNAs often contain IRES so that their mRNAs can still be translated while disrupting translation of host cell mRNA
Some human mRNAs that encode proteins involved in inhibiting apoptosis (cell death) contain (IRES)
Briefly describe the functioning of Bicoid mRNA
Bicoid mRNA is produced and assoc8ates with microtubules at the anterior end of the fruit fly egg
Bicoid protein affects translation of caudal mRNA
Bicoid protein binds Caudal mRNA and inhibits translation
Explain determination of posterior axis of the fruitfly
BCD protein forms a gradient with highest amounts in anterior
Bcd is a transcription factor that activates genes at different concentrations as well as preventing the translation of specific mRNA
Bicoid protein is made at anterior end only and will begin go diffuse across the cell toward the posterior
Describe Bicoid and caudal concentration gradient
Bicoid protein represses caudal mRNA translation
Bicoid protein protein in high concentration where caudal protein concentration in low concentration and vice versa
Explain Bicoid being an interfering protein
Bicoid is an interfering protein: interaction of translation initiation complex with 3’ UTR bound proteins
Proteins like Bicoid (Bcd) can bind to elements in the 3’ UTR that recruit proteins that bind to the m7G cap and prevent binding of the translation initiation complex
What is the role of ferritin in regulation of iron storage?
Ferritin is an iron storage protein
-in low iron: Ferritin mRNA translation is blocked allowing free iron
-in high Iron: ferritin protein is made & excess iron is stored
Without this storage free iron can facilitate the formation of Reactive oxygen species
When you have too much Fe
What is the role of transferrin in iron regulation?
- in low iron: transferrin mRNA is stabilized to allow translation of more transferrin
- in high iron: transferrin mRNA is degraded to reduce protein levels
When you have too little Fe
Explain how interplay between mRNA motifs and binding proteins regulate mRNA
The iron-responsive element (IRE) is a particular hairpin structure located in the 5’ untranslated region (5’-UTR) or in the 3’-untranslated region (3’-UTR) of various mRNAs coding for proteins involved in cellular iron metabolism
The IREs are recognized by trans-acting proteins known as Iron Regulatory Proteins (IRPs) that control mRNA translation rate and stability
Describe binding of competitive inhibitors to iron responsive elements (IRE)(e.g. ferritin-iron storage molecule)
Binding of IRPs sterically hinder the binding of the 40S ribosome
There is competition between iron regulatory proteins (IRP’s) and 40S ribosome for binding to mRNA
Binding of IRP-1 or IRP-2 to IRE prevents binding of ribosome
Therefore no protein is produced and iron is not stored and is free for use in the cell
High iron, iron will bind to IRP so it will no longer bind to IRE and the ribosome will bind .
Protein is produced and iron is stored safely in the cell
