IRE1beta is required for mesoderm formation in Xenopus embryos.
IRE1 is an atypical serine/threonine kinase transmembrane protein with RNase activity. In the unfolded protein response (UPR), they function as proximal sensor of the unfolded proteins in the endoplasmic reticulum (ER). Upon activation by ER stress, IRE1 performs an unconventional cytoplasmic splicing of XBP1 pre-mRNA and thus allows the synthesis of active XBP1, which activates UPR target genes to restore the homeostasis of the ER. IRE1/XBP1 signaling is hence essential for UPR but its function during embryogenesis is yet unknown. The transcripts of the two isoforms of IRE1 in Xenopus, xIRE1alpha and xIRE1beta are differentially expressed during embryogenesis. We found that xIRE1beta is sufficient for cytoplasmic splicing of xXBP1 pre-mRNA. Although gain of xIRE1beta function had no significant effect on Xenopus embryogenesis, overexpression of both, xIRE1beta and xXBP1 pre-mRNA, inhibits activin A induced mesoderm formation, suggesting that an enhanced activity of the IRE1/XBP1 pathway represses mesoderm formation. Surprisingly, while loss of XBP1 function promotes mesoderm formation, the loss of IRE1beta function led to a reduction of mesoderm formation, probably by action of IRE1 being different from the IRE1/XBP1 pathway. Therefore, both gain and loss of function studies demonstrate that IRE1 is required for mesoderm formation in Xenopus embryos.
Yuan
Li
L
Institute of Biochemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Cao
Ying
Y
Oswald
Franz
F
Knöchel
Walter
W
D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D015870:Gene Expression; D008648:Mesoderm / Q000254:growth & development* / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors; D014981:Xenopus / Q000196:embryology*
D004268:DNA-Binding Proteins; C527889:ERN1 protein, Xenopus; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D012260:Ribonucleases