title: A novel long intergenic noncoding RNA indispensable for the cleavage of mouse two-cell embryos.
abstract: 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.
authors: College of Life Science, Northeast Agricultural University, Harbin, China State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Jiaqiang
authors: J
authors: Wang
authors: College of Life Science, Northeast Agricultural University, Harbin, China State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Xin
authors: X
authors: Li
authors: College of Life Science, Northeast Agricultural University, Harbin, China State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Leyun
authors: L
authors: Wang
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Jingyu
authors: J
authors: Li
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Yanhua
authors: Y
authors: Zhao
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Gerelchimeg
authors: G
authors: Bou
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Yufei
authors: Y
authors: Li
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Guanyi
authors: G
authors: Jiao
authors: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors: Xinghui
authors: X
authors: Shen
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Renyue
authors: R
authors: Wei
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Shichao
authors: S
authors: Liu
authors: College of Life Science, Northeast Agricultural University, Harbin, China.
authors: Bingteng
authors: B
authors: Xie
authors: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors: Lei
authors: L
authors: Lei
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Wei
authors: W
authors: Li
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China qzhou@ioz.ac.cn liu086@yahoo.com.
authors: Qi
authors: Q
authors: Zhou
authors: College of Life Science, Northeast Agricultural University, Harbin, China qzhou@ioz.ac.cn liu086@yahoo.com.
authors: Zhonghua
authors: 0000-0002-9199-6493
authors: Z
authors: Liu
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D004265:DNA Helicases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D020077:Endogenous Retroviruses / Q000235:genetics; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D051903:Nuclear Factor 45 Protein / Q000378:metabolism; D011485:Protein Binding; D059367:RNA Cleavage; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D051903:Nuclear Factor 45 Protein; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D004265:DNA Helicases
keywords: 
  ERV
  ; exon skipping; lincRNA; transcription regulation; two‐cell block