Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal
Copyright policy )Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal
mRNA alternative polyadenylation (APA) plays a critical role in post-transcriptional gene control and is highly regulated during development and disease. However, the regulatory mechanisms and functional consequences of APA remain poorly understood. Here, we show that an mRNA 3' processing factor, Fip1, is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Fip1 promotes stem cell maintenance, in part, by activating the ESC-specific APA profiles to ensure the optimal expression of a specific set of genes, including critical self-renewal factors. Fip1 expression and the Fip1-dependent APA program change during ESC differentiation and are restored to an ESC-like state during somatic reprogramming. Mechanistically, we provide evidence that the specificity of Fip1-mediated APA regulation depends on multiple factors, including Fip1-RNA interactions and the distance between APA sites. Together, our data highlight the role for post-transcriptional control in stem cell self-renewal, provide mechanistic insight on APA regulation in development, and establish an important function for APA in cell fate specification.
- University of Iowa United States
- University of California, San Francisco United States
- National Institute of Health Pakistan
- University of California, Irvine United States
- National Institute of Environmental Health Sciences United States
Messenger, Post-Transcriptional, Stem Cell Research - Embryonic - Non-Human, 11 Medical and Health Sciences (for), Regenerative Medicine, Medical and Health Sciences, Regenerative Medicine (rcdc), Mice, Models, 31 Biological sciences (for-2020), Animals (mesh), Developmental, Polyadenylation (mesh), RNA Processing, Post-Transcriptional, 32 Biomedical and Clinical Sciences (for-2020), Stem Cells (mesh), Developmental Biology (science-metrix), Stem Cells, Generic health relevance (hrcs-hc), alternative polyadenylation, Mice (mesh), Gene Expression Regulation, Developmental, Biological Sciences, 06 Biological Sciences (for), Monomeric GTP-Binding Proteins (mesh), Stem Cell Research - Embryonic - Human (rcdc), mRNA processing, Post-Transcriptional (mesh), 570, RNA Processing, 1.1 Normal biological development and functioning, 08 Information and Computing Sciences (for), Developmental (mesh), Biological (mesh), Polyadenylation, Models, Biological, Stem Cell Research - Embryonic - Non-Human (rcdc), 576, Underpinning research, Information and Computing Sciences, Genetics, Animals, RNA, Messenger, Stem Cell Research - Embryonic - Human, Monomeric GTP-Binding Proteins, 1.1 Normal biological development and functioning (hrcs-rac), Messenger (mesh), 31 Biological Sciences (for-2020), Biomedical and Clinical Sciences, Genetics (rcdc), reprogramming, Biological, Stem Cell Research, Stem Cell Research (rcdc), 3101 Biochemistry and Cell Biology (for-2020), stem cell, 32 Biomedical and clinical sciences (for-2020), Gene Expression Regulation, RNA, Biochemistry and Cell Biology, Generic health relevance, Developmental Biology
Messenger, Post-Transcriptional, Stem Cell Research - Embryonic - Non-Human, 11 Medical and Health Sciences (for), Regenerative Medicine, Medical and Health Sciences, Regenerative Medicine (rcdc), Mice, Models, 31 Biological sciences (for-2020), Animals (mesh), Developmental, Polyadenylation (mesh), RNA Processing, Post-Transcriptional, 32 Biomedical and Clinical Sciences (for-2020), Stem Cells (mesh), Developmental Biology (science-metrix), Stem Cells, Generic health relevance (hrcs-hc), alternative polyadenylation, Mice (mesh), Gene Expression Regulation, Developmental, Biological Sciences, 06 Biological Sciences (for), Monomeric GTP-Binding Proteins (mesh), Stem Cell Research - Embryonic - Human (rcdc), mRNA processing, Post-Transcriptional (mesh), 570, RNA Processing, 1.1 Normal biological development and functioning, 08 Information and Computing Sciences (for), Developmental (mesh), Biological (mesh), Polyadenylation, Models, Biological, Stem Cell Research - Embryonic - Non-Human (rcdc), 576, Underpinning research, Information and Computing Sciences, Genetics, Animals, RNA, Messenger, Stem Cell Research - Embryonic - Human, Monomeric GTP-Binding Proteins, 1.1 Normal biological development and functioning (hrcs-rac), Messenger (mesh), 31 Biological Sciences (for-2020), Biomedical and Clinical Sciences, Genetics (rcdc), reprogramming, Biological, Stem Cell Research, Stem Cell Research (rcdc), 3101 Biochemistry and Cell Biology (for-2020), stem cell, 32 Biomedical and clinical sciences (for-2020), Gene Expression Regulation, RNA, Biochemistry and Cell Biology, Generic health relevance, Developmental Biology
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