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
Publisher: Elsevier
: 2017
: Stem Cell Reports
: 8
: 5
: 1442
: 1454
: 13
: 2213-6711
DOI: https://doi.org/10.1016/j.stemcr.2017.04.016
: http://www.sciencedirect.com/science/article/pii/S2213671117301704
: https://research.utu.fi/converis/portal/detail/Publication/24980044
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.