Abstract
Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt of the 3' telomere tail and substantially enhances the catalytic activity and processivity of telomerase. The expression level of hnRNP A2* in tissues positively correlates with telomerase activity, and overexpression of hnRNP A2* leads to telomere elongation in vivo. Thus, hnRNP A2* plays a positive role in unfolding telomere G-quadruplexes and in enhancing telomere extension by telomerase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Animals
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Base Sequence
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Binding Sites / genetics
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Cell Line
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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DNA, Complementary / metabolism
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G-Quadruplexes*
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HeLa Cells
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / chemistry
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
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Humans
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Liver / metabolism
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Male
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Mice
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Models, Biological
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Nucleic Acid Conformation
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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Rats
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Telomerase / antagonists & inhibitors
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Telomerase / genetics
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Telomerase / metabolism*
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Telomere / metabolism*
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Telomere Homeostasis / physiology*
Substances
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DNA, Complementary
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Proteins
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hnRNP A2
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Telomerase