RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells

Riikka J. Lund; Nelly Rahkonen; Maia Malonzo; Leni Kauko; Maheswara Reddy Emani; Virpi Kivinen; Elisa Närvä; Esko Kemppainen; Asta Laiho; Heli Skottman; Outi Hovatta; Omid Rasool; Matti Nykter; Harri Lähdesmäki; Riitta Lahesmaa

doi:10.1016/j.stemcr.2017.04.016

RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA⁺ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells

Riikka J. Lund^*, Nelly Rahkonen, Maia Malonzo, Leni Kauko, Maheswara Reddy Emani, Virpi Kivinen, Elisa Närvä, Esko Kemppainen, Asta Laiho, Heli Skottman, Outi Hovatta, Omid Rasool, Matti Nykter, Harri Lähdesmäki, Riitta Lahesmaa

^*Corresponding author for this work

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Abstract

POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA⁺ and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA⁺ transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.

Original language	English
Pages (from-to)	1442-1454
Number of pages	13
Journal	Stem Cell Reports
Volume	8
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2017.04.016
Publication status	Published - 9 May 2017
MoE publication type	A1 Journal article-refereed

Keywords

human embryonic stem cell
mitochondria
pluripotency
polyA RNA
polymerase III
smallRNA
splicing
transcriptome

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10.1016/j.stemcr.2017.04.016

1-s2.0-S2213671117301704-mainFinal published version, 1.84 MBLicence: CC BY

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Lund, R. J., Rahkonen, N., Malonzo, M., Kauko, L., Emani, M. R., Kivinen, V., Närvä, E., Kemppainen, E., Laiho, A., Skottman, H., Hovatta, O., Rasool, O., Nykter, M., Lähdesmäki, H., & Lahesmaa, R. (2017). RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA⁺ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells. Stem Cell Reports, 8(5), 1442-1454. https://doi.org/10.1016/j.stemcr.2017.04.016

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title = "RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells",

abstract = "POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA+ transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.",

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author = "Lund, {Riikka J.} and Nelly Rahkonen and Maia Malonzo and Leni Kauko and Emani, {Maheswara Reddy} and Virpi Kivinen and Elisa N{\"a}rv{\"a} and Esko Kemppainen and Asta Laiho and Heli Skottman and Outi Hovatta and Omid Rasool and Matti Nykter and Harri L{\"a}hdesm{\"a}ki and Riitta Lahesmaa",

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Lund, RJ, Rahkonen, N, Malonzo, M, Kauko, L, Emani, MR, Kivinen, V, Närvä, E, Kemppainen, E, Laiho, A, Skottman, H, Hovatta, O, Rasool, O, Nykter, M, Lähdesmäki, H & Lahesmaa, R 2017, 'RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA⁺ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells', Stem Cell Reports, vol. 8, no. 5, pp. 1442-1454. https://doi.org/10.1016/j.stemcr.2017.04.016

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T1 - RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells

AU - Lund, Riikka J.

AU - Rahkonen, Nelly

AU - Malonzo, Maia

AU - Kauko, Leni

AU - Emani, Maheswara Reddy

AU - Kivinen, Virpi

AU - Närvä, Elisa

AU - Kemppainen, Esko

AU - Laiho, Asta

AU - Skottman, Heli

AU - Hovatta, Outi

AU - Rasool, Omid

AU - Nykter, Matti

AU - Lähdesmäki, Harri

AU - Lahesmaa, Riitta

PY - 2017/5/9

Y1 - 2017/5/9

N2 - POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA+ transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.

AB - POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA+ transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.

KW - human embryonic stem cell

KW - mitochondria

KW - pluripotency

KW - polyA RNA

KW - polymerase III

KW - smallRNA

KW - splicing

KW - transcriptome

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DO - 10.1016/j.stemcr.2017.04.016

M3 - Article

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VL - 8

SP - 1442

EP - 1454

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 5

ER -

RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA⁺ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells

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New Insights into Mechanisms Regulating Gene Expression in Embryonic Stem Cells

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RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells

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Keywords

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New Insights into Mechanisms Regulating Gene Expression in Embryonic Stem Cells

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RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA⁺ and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells