The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines.
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 pre-mRNA may influence mitochondrial biogenesis under variable physiological conditions and could play a role in distinct mitochondrial diseases.
Department of Neurology, University of Amsterdam, The Netherlands.
J N
JN
Spelbrink
C
C
Van den Bogert
D017398:Alternative Splicing; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D051265:NF-E2-Related Factor 1; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051265:NF-E2-Related Factor 1; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D012322:RNA Precursors; D012333:RNA, Messenger; D015534:Trans-Activators