Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells

Molecular Cell
Aishe A SarshadMarkus Hafner

Abstract

In mammals, gene silencing by the RNA-induced silencing complex (RISC) is a well-understood cytoplasmic posttranscriptional gene regulatory mechanism. Here, we show that embryonic stem cells (ESCs) contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO protein activity allows for the onset of differentiation. In the nucleus, AGO proteins interact with core RISC components, including the TNRC6 proteins and the CCR4-NOT deadenylase complex. In contrast to cytoplasmic miRNA-mediated gene silencing that mainly operates on cis-acting elements in mRNA 3' untranslated (UTR) sequences, in the nucleus AGO binding in the coding sequence and potentially introns also contributed to post-transcriptional gene silencing. Thus, nuclear localization of AGO proteins in specific cell types leads to a previously unappreciated expansion of the miRNA-regulated transcriptome.

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Citations

Nov 16, 2019·Nature Reviews. Genetics·Noa Gil, Igor Ulitsky
Jan 23, 2020·Journal of Cellular Physiology·Thomas BeiterDirk Moser
Feb 23, 2020·International Journal of Molecular Sciences·Tomoko Takahashi, Kumiko Ui-Tei
Jan 24, 2020·Mini Reviews in Medicinal Chemistry·Srijit DasDennis Kheng Zhou
Jul 19, 2019·Scientific Reports·Tiia A TurunenMikko P Turunen
Nov 7, 2019·International Journal of Molecular Sciences·Mirza Muhammad Fahd QadirRicardo Luis Pastori
Feb 11, 2020·Frontiers in Cell and Developmental Biology·Madlen MüllerConstance Ciaudo
Sep 4, 2020·International Journal of Molecular Sciences·Giuseppina DivisatoSilvia Parisi
Nov 20, 2019·Nucleic Acids Research·Phillip J KennyStephanie Ceman
Nov 23, 2019·Cells·Christiaan J Stavast, Stefan J Erkeland
Dec 2, 2020·DNA and Cell Biology·Jun TaoZuo Wang
May 19, 2019·Cancer Research·Bruna Rodrigues MuysWilson A Silva
Feb 13, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Paulina Pei Suu TanYuh-Fen Pung
Jan 16, 2021·Life Sciences·Ravichandran Jayasuriya, Kunka Mohanram Ramkumar
Mar 7, 2021·Cancers·Iwona Nowak, Aishe A Sarshad
Sep 6, 2020·Life Sciences·Aysan SalamatiBahman Yousefi
Jul 10, 2021·Frontiers in Molecular Biosciences·Lingyu GuanAndrey Grigoriev
Jul 22, 2021·Biochemistry. Biokhimii︠a︡·Ekaterina V SeminaKseniya A Rubina
Dec 18, 2021·Development·Huanqing ZhangDavid L Turner
Jan 21, 2022·Nucleic Acids Research·Arianna Di FazioMonika Gullerova

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