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Stem Cell Reports. 2017 May 9;8(5):1442-1454. 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.

Author information

1
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland. Electronic address: riikka.lund@utu.fi.
2
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
3
Department of Computer Science, Aalto University, Espoo 02150, Finland.
4
Faculty of Medicine and Life Sciences, BioMediTech, University of Tampere, Tampere 33014, Finland.
5
Department CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 171 77, Sweden.
6
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland; Faculty of Medicine and Life Sciences, BioMediTech, University of Tampere, Tampere 33014, Finland.
7
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland; Department of Computer Science, Aalto University, Espoo 02150, Finland.

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

PMID:
28494942
PMCID:
PMC5425787
DOI:
10.1016/j.stemcr.2017.04.016
[Indexed for MEDLINE]
Free PMC Article

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