| RRC ID |
85344
|
| Author |
Li C, Tan YP, Gao D, Su R, Xu K, Liu SC, Li XF, Lu YH, Yi LT, Wang G, Ou XH, Meng TG, Sun QY.
|
| Title |
IRE1α RNase activity is critical for early embryo development by degrading maternal transcripts.
|
| Journal |
Nucleic Acids Res
|
| Abstract |
During maternal-to-zygotic transition, oocytes and embryos undergo massive maternal mRNA degradation. Three key events are related to RNA degradation: oocyte meiotic resumption, fertilization, and zygotic genome activation (ZGA). In this study, we unexpectedly discover that the UPR (unfolded protein response) protein IRE1α is critical for post-fertilization maternal messenger mRNA (mRNA) degradation. IRE1α is specifically expressed from the metaphase II oocytes to four-cell embryos, with its translation dependent on the ERK1/2 pathway. Oocyte-specific deletion of the IRE1α RNase domain resulted in female infertility, characterized by embryonic developmental arrest at the one-cell or two-cell stage, and failure to degrade maternal mRNAs destined for elimination. Using IRE1α-Flag knock-in mouse model and LACE-seq, as well as in vitro analysis, we show that IRE1α can directly bind and cleave maternal mRNAs after fertilization. Moreover, IRE1α-mediated mRNA decay is essential for ZGA and histone modifications. This study unveils an important function of IRE1α in early embryonic development through regulated IRE1α-dependent decay, independent of the canonical IRE1α-XBP1 signaling pathway, thereby revealing a novel molecular mechanism underlying maternal mRNA degradation triggered by fertilization.
|
| Volume |
53(11)
|
| Published |
2025-6-6
|
| DOI |
10.1093/nar/gkaf520
|
| PII |
8166792
|
| PMID |
40530690
|
| PMC |
PMC12203788
|
| MeSH |
Animals
Embryonic Development* / genetics
Endoribonucleases* / genetics
Endoribonucleases* / metabolism
Female
Gene Expression Regulation, Developmental
Mice
Oocytes / metabolism
Protein Serine-Threonine Kinases* / genetics
Protein Serine-Threonine Kinases* / metabolism
RNA Stability*
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Messenger, Stored* / genetics
RNA, Messenger, Stored* / metabolism
Unfolded Protein Response / genetics
X-Box Binding Protein 1 / metabolism
Zygote / metabolism
|
| IF |
11.502
|
| Resource |
| Mice |
RBRC05515 |
