Graphical AbstractHighlights d LincGET is asymmetrically expressed in the nucleus of twoto four-cell mouse embryos d LincGET overexpression biases blastomere fate toward inner cell mass (ICM) d LincGET physically binds to CARM1 d LincGET/CARM1 activates ICM-specific genes
In BriefAn endogenous retrovirus-associated nuclear long noncoding RNA biases cell fate in mouse two-cell embryos.
Endogenous retroviruses (ERVs) are transcriptionally active in cleavage stage embryos, yet their functions are unknown. ERV sequences are present in the majority of long intergenic noncoding RNAs (lincRNAs) in mouse and humans, playing key roles in many cellular processes and diseases. Here, we identify LincGET as a nuclear lincRNA that is GLN-, MERVL-, and ERVK-associated and essential for mouse embryonic development beyond the two-cell stage. LincGET is expressed in late two- to four-cell mouse embryos. Its depletion leads to developmental arrest at the late G2 phase of the two-cell stage and to MAPK signaling pathway inhibition. LincGET forms an RNA-protein complex with hnRNP U, FUBP1, and ILF2, promoting the cis-regulatory activity of long terminal repeats (LTRs) in GLN, MERVL, and ERVK (GLKLTRs), and inhibiting RNA alternative splicing, partially by downregulating hnRNP U, FUBP1, and ILF2 protein levels. Hnrnpu or Ilf2 mRNA injection at the pronuclear stage also decreases the preimplantation developmental rate, and Fubp1 mRNA injection at the pronuclear stage causes a block at the two-cell stage. Thus, as the first functional ERV-associated lincRNA, LincGET provides clues for ERV functions in cleavage stage embryonic development.
Proper chromosome segregation during meiosis requires cyclins associated with cyclin-dependent kinases. Li et al. generate Ccnb3 mutant mice via CRISPR/Cas9 and identify a requirement for cyclin B3 in female meiosis I.
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