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Location of 3' and 5' UTR
- both located on mRNA
- 3' is LONGER (before Poly A tail)
- 5' is shorter (after 5'cap)
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mRNA transport types
- active transport: hard to show, but thought that mRNA transports by attaching to cytoskeletal motors. This is thought if mRNA move at faster speeds than diffusion
- passive diffusion: can diffuse through cytoplasm until trapped by localized anchor
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mRNA localization
- via cis-acting elements: these are almost always in 3' UTR,so not to interfere with translation
- cis-acting localization SIGNALS (ie certain nucleotide sequence elements) recognized by RNA-binding proteins that attach it to localization machinery
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Role of 3' and 5' UTR
- Act in mechanisms for localization of mRNA
- Exampple is gurken mRNA, localized in drosophila nucleus
- 3' UTR region of gurken mRNA: K10 gene activity aids in degradation and relocalization of wrongly localized grk mRNA
- 5' UTR region of gurken mRNA: GLE1 required for binding of mRNA to nuc. membrane OR ER. GLE2 stabilizes grk mRNA by inducing translation
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Example of active trasnsport
- Myosin-mediated mRNA transport
- motor is: Myo4 (aka She1)
- mRNA is: ASH1
- 4 cis-acting localization elements
- interaction proteins: She2 and She3
- Mechanism: She2 binds to each of the 4 cis-aacting localization elements
- The RNA binding increases affinity for She3, which binds to Myo4
- MAIN IDEA: Myo4 MOTOR is attached to RNA by She2 and She3 adaptor proteins
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Deadenylation
- mRNA degradation usually initiates with removal of 3' poly A tail.
- Deadenylation results in NON-TRANSLATABLE mRNA protein complexes: mRNPs
- Deadenylation mediated by two different poly A nuclease complexes: Pan2 and Pan3
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Role of Pan2 and Pan3
- These are 2 Poly a nucleases complexes that deadenylate mammalian mRNA
- These nuclease complexes INITIATE shortening of tails to 110nt
- Following this are two other complexes that further shortening of tail
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Decapping
- After deadenylation, 2 pathways can be taken to further DEGRADE mRNA
- 1. 5'->3' decay pathway. mRNA is DECAPPED to expose monophosphorylated 5' end
- Decapping important for DECAY of mRNA from 5'end
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Role of Dcp1p and Dcp2p
- Dcp2p protein is a MAJOR mRNA decapping enzyme
- Dcp1p INTERACTS with Dcp2p, enhancing decapping Activity
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Decay enzymes
AFTER Deadenylation And Decapping: decay enzymes can further decay mRNA in BOTH 3-5' or 5-3' direction
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Role of Xrn1
- This is a DECAY enzyme
- Actins in 5'-->3' direction
- Decapping NECESSARY for this enzyme, as:
- Enzyme prefers the MONO-phosphate end and RESISTS the Capped 5' end
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Alternate decay pathway: miRNA
- these are short RNAs that are partially complementary to mRNA
- Bind to target mRNA and impair its function as template for translation
- May also direct rapid deadenylation
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