Computational modeling and experimental analysis of nonsense-mediated decay in yeast

Dan Cao1, Roy Parker

  • 1Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721, USA.

Cell
|May 22, 2003
PubMed

Insights

Nonsense-mediated decay (NMD) degrades faulty mRNAs in yeast. This study reveals NMD triggers accelerated deadenylation and deadenylation-independent decapping, with 5' nonsense codons showing faster decapping rates.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Eukaryotic cells possess a surveillance system called nonsense-mediated decay (NMD).
  • NMD degrades messenger RNAs (mRNAs) with premature stop codons, ensuring gene expression fidelity.
  • This process prevents the translation of aberrant mRNAs into truncated proteins.

Purpose of the Study:

  • To define mRNA turnover alterations induced by NMD in yeast.
  • To elucidate the mechanistic basis of NMD's polar effect.
  • To develop a computational model for NMD.

Main Methods:

  • Computational modeling
  • Experimental analysis of mRNA turnover
  • Analysis of NMD in yeast

Main Results:

  • Nonsense-containing transcripts are recognized and targeted for deadenylation-independent decapping.
  • NMD accelerates deadenylation irrespective of nonsense codon position.
  • 5' nonsense codons lead to faster decapping rates than 3' nonsense codons.

Conclusions:

  • NMD efficiently degrades aberrant transcripts in yeast.
  • The position of nonsense codons influences NMD kinetics, explaining the polar effect.
  • A computational model accurately describes and predicts NMD processes.

Related Concept Videos

Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...