Functions of paralogous RNA polymerase III subunits POLR3G and POLR3GL in mouse development

Xiaoling Wang, Alan Gerber, Wei-Yi Chen, Robert G. Roeder*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Mammalian cells contain two isoforms of RNA polymerase III (Pol III) that differ in only a single subunit, with POLR3G in one form (Pol IIIα) and the related POLR3GL in the other form (Pol IIIβ). Previous research indicates that POLR3G and POLR3GL are differentially expressed, with POLR3G expression being highly enriched in embryonic stem cells (ESCs) and tumor cells relative to the ubiquitously expressed POLR3GL. To date, the functional differences between these two subunits remain largely unexplored, especially in vivo. Here, we show that POLR3G and POLR3GL containing Pol III complexes bind the same target genes and assume the same functions both in vitro and in vivo and, to a significant degree, can compensate for each other in vivo. Notably, an observed defect in the differentiation ability of POLR3G knockout ESCs can be rescued by exogenous expression of POLR3GL. Moreover, whereas POLR3G knockout mice die at a very early embryonic stage, POLR3GL knockout mice complete embryonic development without noticeable defects but die at about 3 wk after birth with signs of both general growth defects and potential cerebellum-related neuronal defects. The different phenotypes of the knockout mice likely reflect differential expression levels of POLR3G and POLR3GL across developmental stages and between tissues and insufficient amounts of total Pol III in vivo.
Original languageEnglish
Pages (from-to)15702-15711
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
Early online date23 Jun 2020
Publication statusPublished - 7 Jul 2020


FundersFunder number
National Cancer InstituteR01CA129325, CA202245
Human Frontier Science ProgramLT001083/2014
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungP2GEP3_151952


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