Related Experiment Video

Updated: Aug 14, 2026

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events
10:59

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events

Published on: May 13, 2019

Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover

Akio Yamashita1, Tsung-Cheng Chang, Yukiko Yamashita

  • 1Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77030, USA.

Nature Structural & Molecular Biology
|November 15, 2005
PubMed

Insights

Deadenylation by PAN2 and CCR4 enzymes initiates mRNA decay in mammalian cells. Decapping by DCP2 acts as a backup, revealing a link between these mRNA decay pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cytoplasmic mRNA decay pathways in mammalian cells are not fully understood.
  • Enzymatic regulation of mRNA stability is crucial for gene expression control.

Purpose of the Study:

  • To investigate the roles of deadenylation and decapping enzymes in mammalian mRNA decay.
  • To define the sequence and interplay of enzymatic activities in cytoplasmic mRNA decay.

Main Methods:

  • Disruption of deadenylating and decapping enzyme activities in mouse NIH3T3 fibroblasts.
  • Monitoring mRNA decay kinetics and trapping decay intermediates.

Main Results:

  • Deadenylation is the primary step triggering decay for both stable and unstable beta-globin mRNAs.
  • PAN2 initiates deadenylation, followed by CCR4-mediated poly(A) shortening, exhibiting biphasic kinetics.
  • DCP2-mediated decapping occurs post-deadenylation, potentially acting as a backup mechanism.

Conclusions:

  • PAN2 and CCR4 are key cytoplasmic poly(A) nucleases involved in mammalian mRNA deadenylation.
  • DCP2-mediated decapping is functionally linked to deadenylation and contributes to mRNA decay pathways.
  • This study elucidates in vivo pathways for mammalian cytoplasmic mRNA decay.

More Related Videos

Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro09:16

Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro

Published on: May 3, 2014

Identification of Footprints of RNA:Protein Complexes via RNA Immunoprecipitation in Tandem Followed by Sequencing (RIPiT-Seq)09:26

Identification of Footprints of RNA:Protein Complexes via RNA Immunoprecipitation in Tandem Followed by Sequencing (RIPiT-Seq)

Published on: July 10, 2019

Related Concept Videos

mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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.
Cis-acting Elements involved in mRNA stability
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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.
Cis-acting Elements involved in mRNA stability
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...
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,...