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Transient inhibition of rDNA transcription in donor cells improves ribosome biogenesis and preimplantation development of embryos derived from somatic cell nuclear transfer
Author(s) -
Liao Chen,
Pang Nan,
Liu Zhaojun,
Lei Lei
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000025rr
Subject(s) - ribosome biogenesis , somatic cell nuclear transfer , nucleolus , somatic cell , microbiology and biotechnology , biology , embryo , blastocyst , embryogenesis , ribosome , genetics , gene , rna , cytoplasm
Ribosomal DNA (rDNA) transcription is a limiting step in ribosome biogenesis, crucial for protein synthesis and cell growth—especially at the early stages of embryonic development—and is regulated in a mammalian target of rapamycin (mTOR)‐dependent manner. Our previous report demonstrated that treatment with mTOR inhibitors during artificial embryonic activation improved the development of embryos derived from somatic cell nuclear transfer (SCNT). We hypothesize that inhibition of ribosome biogenesis in somatic cells facilitates reactivation of embryonic nucleolar establishment and ribosome biogenesis in SCNT embryos. Herein, we show that mTOR inhibitors suppressed ribosome biogenesis in somatic cells, and more importantly, improved development potential of SCNT embryos (blastocyst rate, 34% vs 24%). SCNT embryos derived from drug‐treated somatic cells exhibited higher levels of 47S, 18S, and 5S rRNAs, upstream binding factor (UBF) mRNA, ribosomal protein S6; they also improved the rebuilding of the nucleolar ultrastructure. In addition, treatment of donor cells with the RNA polymerase I (Pol I) inhibitor cx5461 caused similar effects on SCNT embryos. These results indicated that transient inhibition of rDNA transcription in donor cells facilitated the establishment of functional nucleoli and improved preimplantation development of SCNT embryos.