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Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
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Published on: December 17, 2012

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Nonsense-mediated mRNA decay of mRNAs encoding a signal peptide occurs primarily after mRNA targeting to the

Min-Kyung Shin1, Jeeyoon Chang2, Joori Park1

  • 1Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.

Molecules and Cells
|March 21, 2024
PubMed

Insights

CENTRE, a pathway involving the nuclear cap-binding complex (CBC), translationally represses messenger ribonucleic acids (mRNAs) targeting the endoplasmic reticulum (ER). This repression prevents premature nonsense-mediated mRNA decay (NMD) until ER targeting is complete.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Expression Regulation

Background:

  • Translation of mRNAs for integral membrane or secreted proteins occurs at the endoplasmic reticulum (ER).
  • The signal recognition particle (SRP) targets ribosome-nascent chain complexes (RNCs) to the ER surface.
  • ER targeting involves a quality control pathway known as CENTRE (CBC-ensured translational repression of RNC-SRP).

Purpose of the Study:

  • To investigate the role of CENTRE in regulating the translation and stability of mRNAs encoding ER-targeted proteins.
  • To elucidate the interplay between CENTRE and nonsense-mediated mRNA decay (NMD) during ER targeting.

Main Methods:

  • Ribosome profiling of CBC-associated and eukaryotic translation initiation factor 4E (eIF4E)-associated mRNAs.
  • Analysis of mRNA decay pathways in relation to ER targeting.

Main Results:

  • CENTRE translationally represses CBC-RNC-SRP complexes at the transcriptomic level until ER delivery.
  • CENTRE inhibits NMD of mRNAs within the CBC-RNC-SRP complex.
  • NMD is activated only after ER targeting and replacement of CBC by eIF4E.

Conclusions:

  • CENTRE provides pre-delivery translational control of ER-targeted mRNAs.
  • NMD acts as a post-delivery quality control mechanism for these mRNAs.
  • Dual surveillance ensures proper targeting and quality of mRNAs encoding integral membrane or secretory proteins to the ER.
Keywords:
Cap-binding complexEndoplasmic reticulumEukaryotic translation initiation factor 4ENonsense-mediated messenger RNA decaySignal recognition particle

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