Genomic organization and restricted expression of the human Mona/Gads gene suggests regulation by two specific promoters

Abstract

Monocytic adaptor (Mona) also known as Gads is a Grb2-related adaptor whose expression is restricted to hematopoietic cells. It plays an important role in intracellular signaling in T cells, monocytic cells, and platelets. Here we investigated the regulatory aspects of Mona expression in human hematopoietic cells. This was carried out by combining nucleotide sequence analyzes and experimental approaches. We confirmed that Mona expression is restricted to T-cell, myeloid and platelet lineages. In the various cells examined, we detected two major Mona transcripts (1.9 and 4 kb), likely resulting from the alternative use of two polyadenylation sites. Consequently, Mona transcripts of the same size have identical 3' untranslated region (UTR), irrespective of the cell type. In contrast, Mona transcripts contain either 5' UTR-1A or -1B exons, that were detected in a cell-lineage specific manner. Thus, T cells and several myeloid cell lines express 5' UTR-1A-containing transcripts, whereas platelets and cell lines exhibiting megakaryocytic potential express 5' UTR-1B-containing transcripts. Interestingly, 5' UTR-1A is generated from an exon located approximately 45 kb upstream of exon 1B. This suggested that lineage-restricted transcription of the Mona gene is controlled by specific promoters. Indeed, 2-kb genomic fragments upstream of each 5'-UTR showed lineage-restricted ability to drive expression of luc reporter gene.