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Related Concept Videos

Nuclear Export of mRNA02:31

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Nonsense-mediated mRNA Decay02:27

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Related Experiment Video

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Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection
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Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts.

Nicola Meola1, Michal Domanski1, Evdoxia Karadoulama2

  • 1Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus C, Denmark.

Molecular Cell
|November 23, 2016
PubMed
Summary

The RNA exosome degrades nuclear RNA. New research reveals the poly(A) tail exosome targeting (PAXT) connection, involving ZFC3H1 and PABPN1, which targets processed transcripts, distinct from the NEXT complex.

Keywords:
NEXT complexPAXT connectionRNA exosomenuclear RNA decaypoly(A) tail

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • RNA Biology

Background:

  • The RNA exosome is crucial for RNA degradation in eukaryotic nuclei.
  • Co-factors like Mtr4p/hMTR4 link the exosome to RNA-binding protein adaptors for substrate targeting.
  • The human nuclear exosome targeting (NEXT) complex, including hMTR4, ZCCHC8, and RBM7, targets early, unprocessed transcripts.

Purpose of the Study:

  • To elucidate the mechanism by which the nuclear exosome recognizes and targets processed RNA transcripts.
  • To identify novel targeting mechanisms beyond the known NEXT complex.
  • To understand how different RNA maturation states are recognized by the nuclear exosome.

Main Methods:

  • Depletion studies of ZFC3H1 and PABPN1.
  • Analysis of RNA transcript accumulation and polyadenylation status.
  • Investigation of protein-protein interactions between exosome co-factors and adaptors.

Main Results:

  • A novel poly(A) tail exosome targeting (PAXT) connection was identified, linking hMTR4 to ZFC3H1 and PABPN1.
  • Depletion of ZFC3H1 or PABPN1 led to the accumulation of longer, more polyadenylated transcripts compared to NEXT substrates.
  • ZFC3H1/PABPN1 and ZCCHC8/RBM7 interact with hMTR4 in a mutually exclusive manner.

Conclusions:

  • The nuclear exosome utilizes distinct adaptor complexes to target RNAs based on their maturation status.
  • The PAXT connection targets processed, polyadenylated RNAs, while NEXT targets unprocessed RNAs.
  • Substitution of hMTR4-associating adaptors allows the exosome to discriminate between different RNA substrates.