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Nucleic Acids Research 2005 33(2):486-496; doi:10.1093/nar/gki203
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Published online 19 January 2005

© 2005, the authors Nucleic Acids Research, Vol. 33 No. 2 © Oxford University Press 2005; all rights reserved
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Article

hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere

Kim Moran-Jones, Lyndal Wayman1, Derek D. Kennedy2, Roger R. Reddel1, Sergio Sara, Mark J. Snee and Ross Smith*

Department of Biochemistry and Molecular Biology, The University of Queensland QLD 4072, Australia 1 Children's Medical Research Institute 214 Hawkesbury Road, Westmead, NSW 2145, Australia 2 School of Biomolecular and Biomedical Sciences, Griffith University Nathan, QLD 4111, Australia

*To whom correspondence should be addressed. Tel: +61 7 3365 4627; Fax: +61 7 3365 4699; Email: ross.s{at}uq.edu.au

Received November 16, 2004. Revised December 18, 2004. Accepted December 31, 2004.

The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a multi-tasking protein that acts in the cytoplasm and nucleus. We have explored the possibility that this protein is associated with telomeres and participates in their maintenance. Rat brain hnRNP A2 was shown to have two nucleic acid binding sites. In the presence of heparin one site binds single-stranded oligodeoxyribonucleotides irrespective of sequence but not the corresponding oligoribonucleotides. Both the hnRNP A2-binding cis-acting element for the cytoplasmic RNA trafficking element, A2RE, and the ssDNA telomere repeat match a consensus sequence for binding to a second sequence-specific site identified by mutational analysis. hnRNP A2 protected the telomeric repeat sequence, but not the complementary sequence, against DNase digestion: the glycine-rich domain was found to be necessary, but not sufficient, for protection. The N-terminal RRM (RNA recognition motif) and tandem RRMs of hnRNP A2 also bind the single-stranded, template-containing segment of telomerase RNA. hnRNP A2 colocalizes with telomeric chromatin in the subset of PML bodies that are a hallmark of ALT cells, reinforcing the evidence for hnRNPs having a role in telomere maintenance. Our results support a model in which hnRNP A2 acts as a molecular adapter between single-stranded telomeric repeats, or telomerase RNA, and another segment of ssDNA.

Present addresses: K. Moran-Jones, Department of Neurosciences NC30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA

M. Snee, Institute for Cellular and Molecular Biology, University of Texas, 2500 Speedway, Austin, TX 78712, USA


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