The Alkali Light Chains of Human Smooth and Nonmuscle Myosins Are Encoded by a Single Gene: Tissue-specific Expression by Alternative Splicing Pathways

Abstract

Human smooth muscle and nonmuscle cells express closely related myosin alkali light chains which are different from the isoforms present in striated muscle tissues. To date no information on the amino acid sequence of these mammalian nonstriated muscle isoforms has been available. We have isolated full-length cDNA clones encoding the nonmuscle (lym4) and smooth muscle (GT6) myosin light chains (MLCs) from cultured human lymphoblasts and heart aorta smooth muscle cells, respectively. Here we present the complete nucleotide sequences for both cDNA clones, together with the deduced amino acid sequences for the peptides. Both cDNAs contain the same open reading frame for 151 amino acids with 5 amino acid differences located in the C terminus. These differences are encoded by a block of 44 nucleotides which is present only in the smooth muscle (SM) mRNA. To identify the human gene coding for the two MLC isoforms, we have isolated and sequenced the nonmuscle (NM)/SM MLC gene, together with several intronless pseudogenes. A single functional gene was found containing 7 exons which are utilized for the coding information of the SM MLC mRNA. In contrast, the NM MLC mRNA does not contain sequences encoded by exon 6 which corresponds to the 44 nucleotides expressed in SM mRNA. This genomic configuration suggests that both the smooth muscle and nonmuscle MLCs in man are generated from the identical primary transcript by alternative splicing pathways taking place in a tissue-dependent manner.