CAS BI 203 Lecture Notes - Lecture 4: Eif2B, Eif2, Energizer Bunny
22 May 2018
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Translation
- mRNAs can have multiple ribosomes attached to them because they’re pretty long.
These multiple ribosomes create a polysome
Regulation of Translation
Cell have various mechanisms in place to regulate translation at three levels:
1. Translational regulation of specific RNAs
➢Ferritin stores iron in our body. If you don’t have iron, no need to make ferritin. So
it can be regulated based on iron levels.
➢IRE - Iron Response Element - we use UTR regions to regulate translation
➢When there is iron: INSERT NOTES
➢When there isn’t iron: INSERT NOTES
➢You can have the repressors bind to both 5’ and 3’ UTR sequences either way,
the initiation complex can’t be made to start translation
➢Remember: length of poly-A tail regulates translational rates
➢Poly-A binding protein is probably the most important binding protein
➢RNAi can be used to block gene expression (both in body and synthetically we
can make siRNA and they can break down and degrade mRNA) These RNAs are
called microRNAs.
i. Leads to either perfect pairing or mismatched pairing which will cut
perfect or cause adenylation or degradation, respectively.
➢We have about a 1000 human miRNAs and each targets ~100 different mRNAs
➢About ⅓ of human genes regulated by miRNAs
2. “Global” regulation of translation (i.e. of all mRNAs in cell)
➢Controllable by messing with inhibition factors (eIF2 & eIF4E)
➢eIF2 is the first transfer RNA associated with initiation of translation
➢It is regulated by binding to GTP/GDP. So for the reaction occur, eIF2-GTP must
be regenerated.
i. eIF2B(unny) (Energizer Bunny) exchanges GDP for GTP on eIF2. eIF2
and eIF2B are inhibited by phosphorylation when cells in “stressful”
conditions. BOTH get phosphorylated (not only eIF2 but also eIF2B).
➢Also regulated by eIF4E
i. Recognizes 5’ cap. Its regulated by protein-protein interactions with
4E-Binding Protein → Blocks eIF4E interaction with other eIFs and so
blocks translation inhibition.
ii. When growth factors are present, 4e-BP gets phosphorylated.
3. Regulation of where specific mRNAs are translated
➢Xenopus oocytes
i. Xlerk mRNA localized to the “vegetal pole”. It can be labelled blue and
injected into the cell and examine where it localized (IF) it localized.
ii. 3’ UTR sequences are bound by mRNA localization proteins that
transport them to their correct destination.
Document Summary
Mrnas can have multiple ribosomes attached to them because they"re pretty long. Cell have various mechanisms in place to regulate translation at three levels: translational regulation of specific rnas. If you don"t have iron, no need to make ferritin. So it can be regulated based on iron levels. Ire - iron response element - we use utr regions to regulate translation. You can have the repressors bind to both 5" and 3" utr sequences either way, the initiation complex can"t be made to start translation. Remember : length of poly-a tail regulates translational rates. Poly-a binding protein is probably the most important binding protein. Rnai can be used to block gene expression (both in body and synthetically we can make sirna and they can break down and degrade mrna) these rnas are called micrornas. i. Leads to either perfect pairing or mismatched pairing which will cut perfect or cause adenylation or degradation, respectively.
