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

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Abstrakti

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.

Alkuperäiskieli	Englanti
Sivut	1442-1454
Sivumäärä	13
Julkaisu	Stem Cell Reports
Vuosikerta	8
Numero	5
DOI - pysyväislinkit	https://doi.org/10.1016/j.stemcr.2017.04.016
Tila	Julkaistu - 9 toukok. 2017
OKM-julkaisutyyppi	A1 Julkaistu artikkeli, soviteltu

Pääsy asiakirjaan

10.1016/j.stemcr.2017.04.016

1-s2.0-S2213671117301704-mainFinal published version, 1,84 MBLisenssi: CC BY

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Link to publication in Scopus

New Insights into Mechanisms Regulating Gene Expression in Embryonic Stem Cells
Harri Lähdesmäki
31/05/2017
1 kohde/ Medianäkyvyys
Lehdistö/media: Esiintyminen mediassa

Siteeraa tätä

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

@article{1653a34a0ff24878b56d4fc4f7f522ad,

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.",

keywords = "human embryonic stem cell, mitochondria, pluripotency, polyA RNA, polymerase III, smallRNA, splicing, transcriptome",

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",

year = "2017",

month = may,

day = "9",

doi = "10.1016/j.stemcr.2017.04.016",

language = "English",

volume = "8",

pages = "1442--1454",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

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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, Vuosikerta 8, Nro 5, Sivut 1442-1454. https://doi.org/10.1016/j.stemcr.2017.04.016

TY - JOUR

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

UR - http://www.scopus.com/inward/record.url?scp=85019433296&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2017.04.016

DO - 10.1016/j.stemcr.2017.04.016

M3 - Article

AN - SCOPUS:85019433296

VL - 8

SP - 1442

EP - 1454

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 5

ER -