A brain-specific pgc1α fusion transcript affects gene expression and behavioural outcomes in mice
Open Access
- 14 October 2021
- journal article
- Published by Life Science Alliance, LLC in Life Science Alliance
- Vol. 4 (12), e202101122
- https://doi.org/10.26508/lsa.202101122
Abstract
PGC1α is a transcriptional coactivator in peripheral tissues, but its function in the brain remains poorly understood. Various brain-specific Pgc1α isoforms have been reported in mice and humans, including two fusion transcripts (FTs) with non-coding repetitive sequences, but their function is unknown. The FTs initiate at a simple sequence repeat locus ∼570 Kb upstream from the reference promoter; one also includes a portion of a short interspersed nuclear element (SINE). Using publicly available genomics data, here we show that the SINE FT is the predominant form of Pgc1α in neurons. Furthermore, mutation of the SINE in mice leads to altered behavioural phenotypes and significant up-regulation of genes in the female, but not male, cerebellum. Surprisingly, these genes are largely involved in neurotransmission, having poor association with the classical mitochondrial or antioxidant programs. These data expand our knowledge on the role of Pgc1α in neuronal physiology and suggest that different isoforms may have distinct functions. They also highlight the need for further studies before modulating levels of Pgc1α in the brain for therapeutic purposes.Funding Information
- Intramural Research Program
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (Moy SS U54 HD079124)
- Chilean National Agency for Research and Development (Hernandez B 21201090)
- FONDECYT (Riadi G 11140869)
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