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 process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative modulator of autophagy. Our findings suggest that the alternative splicing of Beclin 1 might play important roles in leukemogenesis regulated by autophagy.
Hematology Center of Cyrus Tang Medical Institute, Affiliated Changshu Hospital, School of Medicine, Soochow University, Suzhou, China E-mail : jrwang@suda.edu.cn, niuyuna@suda.eud.cn.
Yu-Na
YN
Niu
Qing-Qing
QQ
Liu
Su-Ping
SP
Zhang
Na
N
Yuan
Yan
Y
Cao
Jin-Yang
JY
Cai
Wei-Wei
WW
Lin
Fei
F
Xu
Zhi-Jian
ZJ
Wang
Bo
B
Chen
Jian-Rong
JR
Wang
D017398:Alternative Splicing / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D000071186:Beclin-1; D002460:Cell Line; D045744:Cell Line, Tumor; D005091:Exons / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger