RNA transport and stability and decay.txt

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Author:
rincrocci
ID:
143973
Filename:
RNA transport and stability and decay.txt
Updated:
2012-03-26 15:25:42
Tags:
mRNA transport stability decay
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mRNA transport, stability and decay
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  1. Location of 3' and 5' UTR
    • both located on mRNA
    • 3' is LONGER (before Poly A tail)
    • 5' is shorter (after 5'cap)
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. Role of Dcp1p and Dcp2p
    • Dcp2p protein is a MAJOR mRNA decapping enzyme
    • Dcp1p INTERACTS with Dcp2p, enhancing decapping Activity
  10. Decay enzymes
    AFTER Deadenylation And Decapping: decay enzymes can further decay mRNA in BOTH 3-5' or 5-3' direction
  11. 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
  12. 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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