P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes
Many non-coding RNAs (ncRNAs) serve as regulatory molecules in various physiological pathways, including gene expression in mammalian cells. Distinct from protein-coding RNA expression, ncRNA expression is regulated solely by transcription and RNA processing/stability. It is thus important to unders...
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doaj-62ef02a8217f49d691de59070624a6ab2020-11-25T01:49:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-04-011010.3389/fgene.2019.00342450129P-TEFb Regulates Transcriptional Activation in Non-coding RNA GenesHeeyoun Bunch0Hyeseung Choe1Jongbum Kim2Doo Sin Jo3Soyeon Jeon4Sanghwa Lee5Dong-Hyung Cho6Keunsoo Kang7Department of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, South KoreaDepartment of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, South KoreaDepartment of Transcriptome & Epigenome, Macrogen Incorporated, Seoul, South KoreaInstitute of Life Science and Biotechnology, College of Natural Science, Kyungpook National University, Daegu, South KoreaDepartment of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, South KoreaDepartment of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, South KoreaDepartment of Life Science, College of Natural Science, Kyungpook National University, Daegu, South KoreaDepartment of Microbiology, College of Natural Sciences, Dankook University, Cheonan, South KoreaMany non-coding RNAs (ncRNAs) serve as regulatory molecules in various physiological pathways, including gene expression in mammalian cells. Distinct from protein-coding RNA expression, ncRNA expression is regulated solely by transcription and RNA processing/stability. It is thus important to understand transcriptional regulation in ncRNA genes but is yet to be known completely. Previously, we identified that a subset of mammalian ncRNA genes is transcriptionally regulated by RNA polymerase II (Pol II) promoter-proximal pausing and in a tissue-specific manner. In this study, human ncRNA genes that are expressed in the early G1 phase, termed immediate early ncRNA genes, were monitored to assess the function of positive transcription elongation factor b (P-TEFb), a master Pol II pausing regulator for protein-coding genes, in ncRNA transcription. Our findings indicate that the expression of many ncRNA genes is induced in the G0–G1 transition and regulated by P-TEFb. Interestingly, a biphasic characteristic of P-TEFb-dependent transcription of serum responsive ncRNA genes was observed: Pol II carboxyl-terminal domain phosphorylated at serine 2 (S2) was largely increased in the transcription start site (TSS, -300 to +300) whereas overall, it was decreased in the gene body (GB, > +350) upon chemical inhibition of P-TEFb. In addition, the three representative, immediate early ncRNAs, whose expression is dependent on P-TEFb, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear enriched abundant transcript 1 (NEAT1), and X-inactive specific transcript (XIST), were further analyzed for determining P-TEFb association. Taken together, our data suggest that transcriptional activation of many human ncRNAs utilizes the pausing and releasing of Pol II, and that the regulatory mechanism of transcriptional elongation in these genes requires the function of P-TEFb. Furthermore, we propose that ncRNA and mRNA transcription are regulated by similar mechanisms while P-TEFb inhibition unexpectedly increases S2 Pol II phosphorylation in the TSSs in many ncRNA genes.One Sentence Summary: P-TEFb regulates Pol II phosphorylation for transcriptional activation in many stimulus-inducible ncRNA genes.https://www.frontiersin.org/article/10.3389/fgene.2019.00342/fullnon-coding RNARNA polymerase II promoter-proximal pausingP-TEFbgene expression regulationtranscriptional elongation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heeyoun Bunch Hyeseung Choe Jongbum Kim Doo Sin Jo Soyeon Jeon Sanghwa Lee Dong-Hyung Cho Keunsoo Kang |
spellingShingle |
Heeyoun Bunch Hyeseung Choe Jongbum Kim Doo Sin Jo Soyeon Jeon Sanghwa Lee Dong-Hyung Cho Keunsoo Kang P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes Frontiers in Genetics non-coding RNA RNA polymerase II promoter-proximal pausing P-TEFb gene expression regulation transcriptional elongation |
author_facet |
Heeyoun Bunch Hyeseung Choe Jongbum Kim Doo Sin Jo Soyeon Jeon Sanghwa Lee Dong-Hyung Cho Keunsoo Kang |
author_sort |
Heeyoun Bunch |
title |
P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes |
title_short |
P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes |
title_full |
P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes |
title_fullStr |
P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes |
title_full_unstemmed |
P-TEFb Regulates Transcriptional Activation in Non-coding RNA Genes |
title_sort |
p-tefb regulates transcriptional activation in non-coding rna genes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2019-04-01 |
description |
Many non-coding RNAs (ncRNAs) serve as regulatory molecules in various physiological pathways, including gene expression in mammalian cells. Distinct from protein-coding RNA expression, ncRNA expression is regulated solely by transcription and RNA processing/stability. It is thus important to understand transcriptional regulation in ncRNA genes but is yet to be known completely. Previously, we identified that a subset of mammalian ncRNA genes is transcriptionally regulated by RNA polymerase II (Pol II) promoter-proximal pausing and in a tissue-specific manner. In this study, human ncRNA genes that are expressed in the early G1 phase, termed immediate early ncRNA genes, were monitored to assess the function of positive transcription elongation factor b (P-TEFb), a master Pol II pausing regulator for protein-coding genes, in ncRNA transcription. Our findings indicate that the expression of many ncRNA genes is induced in the G0–G1 transition and regulated by P-TEFb. Interestingly, a biphasic characteristic of P-TEFb-dependent transcription of serum responsive ncRNA genes was observed: Pol II carboxyl-terminal domain phosphorylated at serine 2 (S2) was largely increased in the transcription start site (TSS, -300 to +300) whereas overall, it was decreased in the gene body (GB, > +350) upon chemical inhibition of P-TEFb. In addition, the three representative, immediate early ncRNAs, whose expression is dependent on P-TEFb, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear enriched abundant transcript 1 (NEAT1), and X-inactive specific transcript (XIST), were further analyzed for determining P-TEFb association. Taken together, our data suggest that transcriptional activation of many human ncRNAs utilizes the pausing and releasing of Pol II, and that the regulatory mechanism of transcriptional elongation in these genes requires the function of P-TEFb. Furthermore, we propose that ncRNA and mRNA transcription are regulated by similar mechanisms while P-TEFb inhibition unexpectedly increases S2 Pol II phosphorylation in the TSSs in many ncRNA genes.One Sentence Summary: P-TEFb regulates Pol II phosphorylation for transcriptional activation in many stimulus-inducible ncRNA genes. |
topic |
non-coding RNA RNA polymerase II promoter-proximal pausing P-TEFb gene expression regulation transcriptional elongation |
url |
https://www.frontiersin.org/article/10.3389/fgene.2019.00342/full |
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