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

• Published in: Stem cell reports 2017-05, Vol.8 (5), p.1442-1454
• Main Authors: Lund, Riikka J., Rahkonen, Nelly, Malonzo, Maia, Kauko, Leni, Emani, Maheswara Reddy, Kivinen, Virpi, Närvä, Elisa, Kemppainen, Esko, Laiho, Asta, Skottman, Heli, Hovatta, Outi, Rasool, Omid, Nykter, Matti, Lähdesmäki, Harri, Lahesmaa, Riitta
• Format: Article
• Language: English
• Subjects: Cell Line; DNA Polymerase gamma - genetics; DNA Polymerase gamma - metabolism; human embryonic stem cell; Human Embryonic Stem Cells - metabolism; Humans; Induced Pluripotent Stem Cells - metabolism; mitochondria; pluripotency; polyA+ RNA; Polyadenylation; polymerase III; Resource; RNA Polymerase III - genetics; RNA Polymerase III - metabolism; RNA Splicing; RNA, Small Untranslated - genetics; RNA, Small Untranslated - metabolism; smallRNA; splicing; Transcriptome
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.04.016

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. •A specific subset of transcriptome is expressed in POLR3G-dependent manner in hPSCs•The primary function of POLR3G is in the maintenance of transcription•mtDNA polymerase gamma (POLG) is among the direct targets of POLR3G In this article, Lund and colleagues show that RNA polymerase III subunit G (POLR3G) regulates a specific subset of transcriptome in human pluripotent stem cells. The primary function of POLR3G is in the maintenance of transcription. Among the direct targets of POLR3G is mtDNA polymerase γ, with potential importance in maintenance of stem cell state in a POLR3G-dependent manner.