hnRNP A1 associates with telomere ends and stimulates telomerase activity

Zhang, Q. S. , Manche, L., Xu, R. M. , Krainer, A. R. (June 2006) hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA, 12 (6). pp. 1116-28. ISSN 1355-8382 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/16603717
DOI: 10.1261/rna.58806

Abstract

Telomerase is a ribonucleoprotein enzyme complex that reverse-transcribes an integral RNA template to add short DNA repeats to the 3'-ends of telomeres. G-quadruplex structure in a DNA substrate can block its extension by telomerase. We have found that hnRNP A1--which was previously implicated in telomere length regulation--binds to both single-stranded and structured human telomeric repeats, and in the latter case, it disrupts their higher-order structure. Using an in vitro telomerase assay, we observed that depletion of hnRNP A/B proteins from 293 human embryonic kidney cell extracts dramatically reduced telomerase activity, which was fully recovered upon addition of purified recombinant hnRNP A1. This finding suggests that hnRNP A1 functions as an auxiliary, if not essential, factor of telomerase holoenzyme. We further show, using chromatin immunoprecipitation, that hnRNP A1 associates with human telomeres in vivo. We propose that hnRNP A1 stimulates telomere elongation through unwinding of a G-quadruplex or G-G hairpin structure formed at each translocation step.

Item Type: Paper
Uncontrolled Keywords: Base Sequence Cells Cultured Chromatin Immunoprecipitation DNA chemistry/metabolism DNA, Single-Stranded/metabolism Hela Cells Heterogeneous Nuclear Ribonucleoprotein Group A-B metabolism Humans Models, Biological Molecular Sequence Data Protein Binding Telomerase metabolism Telomere metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression > hnRNP
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > sDNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > telomerase
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: CSHL Librarian
Date: June 2006
Date Deposited: 06 Dec 2011 17:11
Last Modified: 09 Apr 2014 15:22
PMCID: PMC1464852
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22950

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