Recognition and elimination of nonsense mRNA

Oliver Mühlemann1, Andrea B Eberle, Lukas Stalder

  • 1Institute of Cell Biology, University of Berne, Baltzerstrasse 4, CH-3012 Bern, Switzerland. oliver.muehlemann@izb.unibe.ch

Insights

Nonsense-mediated mRNA decay (NMD) is a cellular process that degrades faulty mRNAs with premature stop codons. This conserved mechanism regulates gene expression beyond just quality control.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Cellular surveillance prevents the production of faulty gene products.
  • Nonsense-mediated mRNA decay (NMD) is a translation-dependent process that degrades mRNAs with premature translation termination codons (PTCs).
  • NMD prevents the accumulation of potentially harmful C-terminally truncated proteins.

Purpose of the Study:

  • To review recent findings on the conserved mechanism of PTC identification in NMD.
  • To highlight the role of NMD in gene regulation across different model organisms.

Main Methods:

  • Transcriptome profiling of NMD-deficient yeast, Drosophila, and human cells.
  • Analysis of recent research results from various model organisms.

Main Results:

  • NMD regulates 3-10% of all mRNA levels, directly or indirectly.
  • Evidence suggests an evolutionarily conserved mechanism for PTC identification in NMD.
  • NMD's role extends beyond quality control to gene regulation.

Conclusions:

  • NMD is a crucial conserved mechanism for both mRNA quality control and gene regulation.
  • Understanding PTC identification in NMD is vital for comprehending its broader biological functions.

Related Concept Videos

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,...
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...
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...