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Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
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siRNA - Small Interfering RNAs02:30

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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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Related Experiment Video

Updated: Jul 7, 2026

Electrophoretic Mobility Shift Assay (EMSA) for the Study of RNA-Protein Interactions: The IRE/IRP Example
12:44

Electrophoretic Mobility Shift Assay (EMSA) for the Study of RNA-Protein Interactions: The IRE/IRP Example

Published on: December 3, 2014

RNase domains determine the functional difference between IRE1alpha and IRE1beta.

Yusuke Imagawa1, Akira Hosoda, Shin-Ichi Sasaka

  • 1Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.

FEBS Letters
|February 5, 2008
PubMed
Summary

Endoplasmic reticulum (ER) stress triggers cellular responses involving gene regulation and protein synthesis. The RNase domain of IRE1 dictates the specific functions of its isoforms, IRE1alpha and IRE1beta, in managing ER stress.

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Last Updated: Jul 7, 2026

Electrophoretic Mobility Shift Assay (EMSA) for the Study of RNA-Protein Interactions: The IRE/IRP Example
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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Protein Homeostasis

Background:

  • Endoplasmic reticulum (ER) stress disrupts cellular function and homeostasis.
  • Cells activate protective mechanisms, including gene expression and protein synthesis modulation, to cope with ER stress.
  • The IRE1 (Inositol-requiring enzyme 1) pathway, with its isoforms IRE1alpha and IRE1beta, plays a critical role in these responses.

Purpose of the Study:

  • To investigate the role of the RNase domain of IRE1 in determining the distinct functions of its isoforms.
  • To elucidate how IRE1 isoforms differentially regulate cellular responses to ER stress.

Main Methods:

  • In vivo and in vitro analyses were employed to study IRE1 isoform function.
  • Focus on the enzymatic activity and specificity of the RNase domain of IRE1.

Main Results:

  • The RNase domain of IRE1 was identified as the key determinant of functional specificity between IRE1alpha and IRE1beta.
  • IRE1alpha mediates transcriptional upregulation of ER quality control genes via XBP1 splicing.
  • IRE1beta contributes to translational attenuation of protein synthesis during ER stress.

Conclusions:

  • The RNase domain's structure and activity are crucial for the differential roles of IRE1 isoforms in ER stress management.
  • Understanding these specificities provides insight into maintaining ER homeostasis and cellular health under stress.