Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells


Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic processinvolved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagyin leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cellsfrom 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. Newtranscript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletionof exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform wasassessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variabletranscript is generated by alternative 3’ splicing, and its translational product displayed a reduced activity ininduction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negativemodulator of autophagy. Our findings suggest that the alternative splicing of Beclin 1 might play important rolesin leukemogenesis regulated by autophagy.