Alternative splicing of RNAs transcribed from the human c-myb gene.

Abstract

An alternative splicing event in which a portion of the intron bounded by the vE6 and vE7 exons with v-myb homology is included as an additional 363-nucleotide coding exon (termed E6A or coding exon 9A) has been described for normal and tumor murine cells that express myb. We show here that this alternative splicing event is conserved in human c-myb transcripts. In addition, another novel exon (termed E7A or coding exon 10A) is identified in human c-myb mRNAs expressed in normal and tumor cells. Although the myb protein isoform encoded by murine E6A-containing mRNA is larger than the major c-myb protein, the predicted products of both forms of human alternatively spliced myb transcripts are 3'-truncated myb proteins that terminate in the alternative exons. These proteins are predicted to lack the same carboxy-terminal domains as the viral myb proteins encoded by avian myeloblastosis virus and E26 virus. The junction sequences that flank these exons closely resemble the consensus splice donor and splice acceptor sequences, yet the alternative transcripts are less abundant than is the major form of c-myb transcripts. The contribution that alternative splicing events in c-myb expression may make on c-myb function remains to be elucidated.

Truncated c-Myb expression in the human leukemia cell line TK-6

“…As previously shown, HL-60 and MOLT-4 cells contained abundant c-MYB mRNA of normal size (3.8 kb). 28,29 In contrast, TK-6 cells showed a band of 2.0 kb but did not exhibit a transcript of the normal size (Figure 1a). HeLa cells, which are not of hematopoietic origin, did not contain detectable c-MYB transcripts, although all the cell lines examined exhibited similar amounts of ␤-actin mRNA.…”

“…Nucleotide position 1316 of MYB LMC-8 represents the 3′ end of exon 9. 29 The schematic structure of WTK-1 is shown in Figure 3b. 9rY region depicted in Figure 3b showed 90% identity with the repetitive sequence of the human LTR7 element according to a BLASTN homology search.…”

“…29 The shaded box labeled 9iX represents an exon sequence of the mutant gene that is present in intron 9 of the normal gene. The obliquelined box labeled 9rY represents an exon sequence present only in the mutant gene adjacent to the 3′ end of 9iX.…”

Alternative RNA Splicing Produces Multiple Forms of c-Myb with Unique Transcriptional Activities

“…Alternatively spliced c-myb transcripts have been detected in human, mouse, and chicken hematopoietic cells (33,34,40). The best-characterized of these transcripts includes an alternate exon that encodes a variant of c-Myb with a 121-aminoacid in-frame insertion in the transcriptional activation domain (7,32,34,42).…”

“…The best-characterized of these transcripts includes an alternate exon that encodes a variant of c-Myb with a 121-aminoacid in-frame insertion in the transcriptional activation domain (7,32,34,42). Although biological roles for the variant c-Myb proteins remain unclear, alternatively spliced forms of chicken c-myb have increased transcriptional and transforming potential (42).…”