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3 results on '"reprogramming specific alternative splicing"'

1. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

Author

Cheng-Xu Delon Toh, Jun-Wei Chan, Zheng-Shan Chong, Hao Fei Wang, Hong Chao Guo, Sandeep Satapathy, Dongrui Ma, Germaine Yen Lin Goh, Ekta Khattar, Lin Yang, Vinay Tergaonkar, Young-Tae Chang, James J. Collins, George Q. Daley, Keng Boon Wee, Chadi A. EL Farran, Hu Li, Yoon-Pin Lim, Frederic A. Bard, and Yuin-Han Loh

Subjects
human somatic cell reprogramming, genome-wide siRNA screen, SFRS11, reprogramming specific alternative splicing, ZNF207, Biology (General), QH301-705.5
Abstract

Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET) synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

Published
2016
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2. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming.

Author

Toh, Cheng-Xu Delon, Chan, Jun-Wei, Chong, Zheng-Shan, Wang, Hao Fei, Guo, Hong Chao, Satapathy, Sandeep, Ma, Dongrui, Goh, Germaine Yen Lin, Khattar, Ekta, Yang, Lin, Tergaonkar, Vinay, Chang, Young-Tae, Collins, James J., Daley, George Q., Wee, Keng Boon, Farran, Chadi A. EL, Li, Hu, Lim, Yoon-Pin, Bard, Frederic A., and Loh, Yuin-Han

Abstract

Summary Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors ( SMAD3 , ZMYM2 , SFRS11 , SAE1 , and ESET ) synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

3. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

Author

Chadi A. El Farran, Ekta Khattar, Lin Yang, Frederic Bard, Young-Tae Chang, Hu Li, Vinay Tergaonkar, Hao Fei Wang, Keng Boon Wee, Yuin-Han Loh, Cheng Xu Delon Toh, Jun Wei Chan, Germaine Yen Lin Goh, Dongrui Ma, Yoon Pin Lim, George Q. Daley, Zheng Shan Chong, Sandeep Satapathy, Hongchao Guo, James J. Collins, Institute for Medical Engineering and Science, MIT Synthetic Biology Center, Massachusetts Institute of Technology. Department of Biological Engineering, and Collins, James J.

Subjects
0301 basic medicine, RNA Splicing, SFRS11, Biology, human somatic cell reprogramming, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Splicing factor, RNA interference, reprogramming specific alternative splicing, Humans, Epigenetics, Genetic Testing, RNA, Messenger, RNA, Small Interfering, lcsh:QH301-705.5, Cells, Cultured, Genetics, Gene knockdown, Serine-Arginine Splicing Factors, genome-wide siRNA screen, Genome, Human, ZNF207, Cellular Reprogramming, Protein ubiquitination, Exon skipping, 3. Good health, Cell biology, Repressor Proteins, Kinetics, 030104 developmental biology, lcsh:Biology (General), Gene Knockdown Techniques, RNA splicing, RNA Interference, Reprogramming, Microtubule-Associated Proteins
Abstract

Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET) synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries., Singapore. Agency for Science, Technology and Research (grant JCO R09138), Singapore. Agency for Science, Technology and Research (grant JCO R09125), Singapore. Agency for Science, Technology and Research (Investigatorship research award), National Institutes of Health (U.S.) (NIH grant CA196631-01A1), National Institutes of Health (U.S.) (NIH grant 1U54GM114838-01)

Published
2016

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