Different role of functional domains of hTR in DNA binding to telomere and telomerase reconstruction

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Authors: M. Yeo ; S.Y. Rha ; H.C. Jeung ; X.H. Shen ; S.H. Yang ; S.W. An ; J.K. Roh ; H.C. Chung

MeSH: Binding Sites ; DNA/drug effects ; DNA/metabolism ; Humans ; Immunoprecipitation ; Mutation/genetics ; Nucleic Acid Conformation ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/pharmacology ; RNA ; RNA, Long Noncoding ; RNA, Untranslated/chemistry* ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism* ; Telomerase/chemistry* ; Telomerase/genetics ; Telomerase/metabolism* ; Telomere/metabolism* ; Templates, Genetic

Abstract: Even if template sequence of hTR played an essential role in telomere binding, a 326 nucleotide fragment of hTR containing template, pseudoknot, and CR4–5 domains is critical for both binding with telomeric DNA and reconstitution of telomerase activity. A functional study with antisense oligonucleotides suggested that targeted disruption of the template region efficiently abrogated both telomeric DNA binding and telomerase activity, whereas disruption of the CR4–5 region induced only loss of telomerase activity. hTR interacts with telomeric DNA via structural region composed of the template, pseudoknot, and CR4–5 domains, however, each structural domain plays a distinct role in telomere binding and telomerase activity reconstitution.