Interaction of hnRNP A2/B1 isoforms with telomeric ssDNA and the in vitro function.
Overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1 has been reported as a useful marker to detect cancers in early stage, although the biological reason is not clear. A2/B1 proteins were previously reported to bind telomeric DNA repeats. Alternative splicing of A2/B1 gene produces abundant A2, less abundant B1, and testis-specific minor isoforms B0a and B0b. In this study, B1 and B0b that have the N-terminal 12 amino acid insertion were suggested to have higher affinities to telomeric single-stranded DNA (ssDNA) than A2 and B0a. Kinetic analyses using purified B1 and B0b indicated that they interact dynamically with a single array of telomeric repeats. Furthermore, functional assays demonstrated that B1 and B0b bind with telomeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity. A2/B1 proteins, especially B1 and B0b, may function as telomeric ssDNA-binding proteins in cancer and reproductive cells.
Kamma
H
H
Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan. hkamma@md.tsukuba.ac.jp
Fujimoto
M
M
Fujiwara
M
M
Matsui
M
M
Horiguchi
H
H
Hamasaki
M
M
Satoh
H
H
D017398:Alternative Splicing; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D004277:DNA, Single-Stranded; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020033:Protein Isoforms; D012261:Ribonucleoproteins; C439768:hnRNP A2; D019098:Telomerase