Abstract
Human telomeric DNA consists of hundreds to thousands of tandem repeat hexanucleotides (TTAGGG) and is bound by telomere‐associated proteins to form specialized structure that maintains the integrity of chromosome. These telomere‐associated proteins serve as structural and/or regulatory components for telomere functions. Dysfunctional telomeres are known to trigger growth arrest, senescence, and apoptosis. Previously, we have identified hnRNP A3, a poorly understood member of the hnRNPs A/B, as a novel telomere‐associated protein that binds specifically to single‐stranded telomeric DNA. In this study, the DNA‐binding properties of hnRNP A3 in vitro as well as its putative role of telomere maintenance in vivo were investigated. Here, we showed that the minimal binding sequence (MBS) for hnRNP A3 is 5′‐TAGGGTTAGGG‐3′, and the position of MBS in the single‐strand DNA had little or no effect on the binding by hnRNP A3. The consensus binding sequence in the 11‐mer MBS was characterized as 5′‐[T/C]AG[G/T]NN[T/C]AG[G/T]N‐3′. Furthermore, confocal microscopy and chromatin‐immunoprecipitation (ChIP) studies revealed that hnRNP A3 are associated with telomere in vivo. Knocking‐ down the expression of hnRNP A3 had no effect on telomere length maintenance and did not affect cell proliferation capacity. However, overexpression of hnRNPA3 resulted in the production of steady‐state short telomeres in several cell lines. These findings indicate that hnRNP A3 can participate in telomere function and acts as a negative regulator of telomere length maintenance. This work was supported by research grant CMRPD 170541.
Published Version
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