IRE1beta is required for mesoderm formation in Xenopus embryos

Area of Science:

• Cellular Biology
• Developmental Biology
• Molecular Biology

Background:

• IRE1 (inositol-requiring enzyme 1) is a transmembrane kinase and RNase.
• IRE1 acts as a sensor in the endoplasmic reticulum's unfolded protein response (UPR).
• IRE1 splices XBP1 pre-mRNA, enabling UPR target gene activation and ER homeostasis restoration.

Purpose of the Study:

• To investigate the role of IRE1/XBP1 signaling in Xenopus embryogenesis.
• To understand the function of IRE1 isoforms (xIRE1alpha and xIRE1beta) during development.

Main Methods:

• Studied differential expression of xIRE1alpha and xIRE1beta during embryogenesis.
• Performed gain-of-function and loss-of-function studies on xIRE1beta and xXBP1 pre-mRNA.
• Assessed the impact on activin A-induced mesoderm formation in Xenopus embryos.

Main Results:

• xIRE1beta efficiently splices xXBP1 pre-mRNA.
• Overexpression of xIRE1beta and xXBP1 pre-mRNA inhibited mesoderm formation.
• Loss of xIRE1beta function reduced mesoderm formation, suggesting a role independent of XBP1 splicing.

Conclusions:

• IRE1 signaling is essential for mesoderm formation in Xenopus embryos.
• Enhanced IRE1/XBP1 activity represses mesoderm development.
• IRE1 has a critical role in embryogenesis beyond its canonical UPR function.