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A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA

Xinfu Jiao1, Jeong Ho Chang, Turgay Kilic

  • 1Department Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.

Molecular Cell
|March 26, 2013
PubMed

Insights

Mammalian DXO protein degrades improperly capped messenger RNAs (mRNAs), revealing a crucial quality control pathway. This finding highlights the link between mRNA capping and subsequent processing steps.

Area of Science:

  • Molecular Biology
  • RNA Processing
  • Biochemistry

Background:

  • Yeast proteins Rai1 and Dxo1 clear incompletely 5' end-capped messenger RNAs (mRNAs).
  • The mammalian homolog of these proteins, Dom3Z (DXO), was investigated for its role in RNA quality control.

Purpose of the Study:

  • To characterize the enzymatic activities of mammalian DXO.
  • To investigate the role of DXO in pre-mRNA quality control and processing.

Main Methods:

  • Biochemical assays to determine pyrophosphohydrolase, decapping, and exoribonuclease activities of DXO.
  • Cellular studies to assess the degradation of defectively capped pre-mRNAs by DXO.
  • Crystal structure determination of DXO in complex with substrate mimics and products.

Main Results:

  • Mammalian DXO possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities.
  • DXO preferentially degrades defectively capped pre-mRNAs.
  • Incompletely capped pre-mRNAs exhibit inefficient splicing and poor polyadenylation.
  • Crystal structures provide insights into DXO's catalytic mechanism and substrate interactions.

Conclusions:

  • DXO is a central player in a mammalian pre-mRNA 5' end capping quality control mechanism.
  • Proper 5' end capping is intimately linked to subsequent pre-mRNA splicing and polyadenylation.
  • DXO's multifaceted activities ensure the fidelity of pre-mRNA processing.

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