title: Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells.
abstract: Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Kar
authors.forename: Dhurjhoti
authors.initials: D
authors.lastname: Saha
authors.forename: Gunjan
authors.initials: G
authors.lastname: Purohit
authors.forename: Ankita
authors.initials: A
authors.lastname: Singh
authors.forename: Parveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Vinod Kumar
authors.initials: VK
authors.lastname: Yadav
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.forename: Ram Krishna
authors.initials: RK
authors.lastname: Thakur
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism*; D059372:Nucleotide Motifs; D020449:Repetitive Sequences, Amino Acid; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D035341:Telomeric Repeat Binding Protein 2; C517940:NME2 protein, human; D019098:Telomerase