title: In vitro properties of the conserved mammalian protein hnRNP D suggest a role in telomere maintenance.
abstract: Mammalian chromosomes terminate with a 3' tail which consists of reiterations of the G-rich repeat, d(TTAGGG). The telomeric tail is the primer for replication by telomerase, and it may also invade telomeric duplex DNA to form terminal lariat structures, or T loops. Here we show that the ubiquitous and highly conserved mammalian protein hnRNP D interacts specifically with the G-rich strand of the telomeric repeat. A single gene encodes multiple isoforms of hnRNP D. All isoforms bind comparably to the G-rich strand, and certain isoforms can also bind tightly and specifically to the C-rich telomeric strand. G-rich telomeric sequences readily form structures stabilized by G-G pairing, which can interfere with telomere replication by telomerase. We show that hnRNP D binding to the G-rich strand destabilizes intrastrand G-G pairing and that hnRNP D interacts specifically with telomerase in human cell extracts. This biochemical analysis suggest that hnRNP D could function in vivo to destabilize structures formed by telomeric G-rich tails and facilitate their extension by telomerase.
authors.affiliation: Departments of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520-8024, USA.
authors.forename: A
authors.initials: A
authors.lastname: Eversole
authors.forename: N
authors.initials: N
authors.lastname: Maizels
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000378:metabolism; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012261:Ribonucleoproteins / Q000378:metabolism*; D013379:Substrate Specificity; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020033:Protein Isoforms; D012332:RNA, Heterogeneous Nuclear; D012261:Ribonucleoproteins; D019098:Telomerase