© 1995 Oxford University Press
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The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines
Department of Neurology and Department of Biochemistry, Academic Medical Center, University of Amsterdam PO Box 22700, 1100 DE Amsterdam, The Netherlands
*To whom correspondence should be adressed at: Laboratorium Neurozintuigen. Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Received April 18, 1995; Revised June 21, 1995; Accepted June 21, 1995
Nuclear respiratory factor 1 (nrf-1) is a transcriptional activator that is most probably essential in the regulation of mitochondrial biogenesis. In studies of the expression of the NRF-1 gene in cultured human fibroblasts, using RT-PCR, we identified two distinct transcripts, one of which contained an in-frame deletion of 198 bp. Analysis of genomic DNA by sequencing, showed that the shorter mRNA is the result of alternative splicing (exon skipping). The shorter transcript will result in an isoform of the protein that lacks the carboxy-terminal part of the DNA binding domain, which might influence transcriptional activation by normal nrf-1. The alternatively spliced transcript was also present in other human cell lines and in several human tissues. A quantitative PCR analysis showed that the percentages of the alternatively spliced transcript ranged from 3 to 17%. Differences in the percentage of alternatively spliced NRF-1 premRNA may influence mitochondrial biogenesis under variable physiological conditions and could play a role in distinct mitochondrial diseases.