Additional organizational features of the murine folylpolyglutamate synthetase gene - Two remotely situated exons encoding an alternate 5' end and proximal open reading frame under the control of a second promoter

作者：Roy K; Mitsugi K; Sirotnak FM

来源：Journal of Biological Chemistry, 1997, 272(9): 5587-5593.

Nucleotide sequence analysis of independently isolated clones from a mouse liver cDNA library identified two additional splice variants of folylpolyglutamate synthetase (FPGS) mRNA with novel sequence at the 5' end, These variants incorporate two new alternatives (exons Ala and Alb) of exon 1 in the murine FPGS gene which are also spliced to exon 2, Exon Ala encodes most of the 5'-untranslated region, Exon Alb encodes a downstream segment of the 5'-untranslated region, two ATG start codons, and a unique mitochondrial leader peptide as well as 15 additional amino acids of cytosolic FPGS not encoded by all previously identified (Roy, K,, Mitsugi, K,, and Sirotnak, F. M, (1996) J, Biol, Chem,, 271, 23820-23827) splice variants, It was also found by direct sequencing of genomic fragments that although exon Alb is spliced to exon 2, these new alternatives (i.e. exons Ala and Alb) to exon 1 are found approximately 9.5 kilobases upstream from exons Bla, Bib, and B1c, Exons Ala and Alb are separated from each other by a 124-nucleotide intron, Sequencing of the region 5' to exon Ala revealed a nucleotide sequence that was promoter-like and different from the downstream promoter region in the content of putative cis-acting elements, Primer extension analysis identified a number of potential transcription start sites within the more 3' end of this region, FPGS RNA transcripts incorporating exons Ala and Alb were detected in both normal mouse tissues, particularly, liver and kidney, and also to a varying extent in tumors; FPGS RNA transcripts incorporating exons Bla, Bib, and B1c were detected mainly in tumors, Thus, transcription of the FPGS gene in this tissue-specific manner appears to reflect the different usage of alternates to exon 1 under the control of different promoters, An unusual splice variant identified infrequently in a mouse liver cDNA library was 2.67 kilobases in size and incorporated exons Ala and Alb and a segment of the downstream promoter region along with exons B1c and B1b and exons 2-15.

• 出版日期1997-2-28