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Telomeric repeat-containing RNA (referred to as TERRA), a noncoding RNA molecule, has recently been found in mammalian cells. The detailed structural features and function of the TERRA RNA at human chromosome ends remain unclear, although this RNA molecule may be a key component of the telomere machinery. In the present studies, we investigated the structural features of human TERRA RNA in living cells. Using a light-switching pyrene probe, we found that human TERRA RNA forms a parallel G-quadruplex structure in living cells, providing the in vivo evidence for the presence of the G-quadruplex in human TERRA RNA. Furthermore, imaging experiments clearly show that TERRA RNA G-quadruplex localizes to telomere DNA at cell nuclei. These results provide valuable information to allow understanding of the structure and function of human TERRA RNA.telomere biology | telomere RNA | RNA folding | chemical probe

Hepatocyte growth factor (HGF) receptor, also known as Met, is a member of the receptor tyrosine kinase family. The Met–HGF interaction regulates various signalling pathways involving downstream kinases, such as Akt and Erk. Met activation is implicated in wound healing of tissues via multiple biological responses triggered by the above-mentioned signalling cascade. Here we report the development of artificial Met-activating dimeric macrocycles. We identify Met-binding monomeric macrocyclic peptides by means of the RaPID (random non-standard peptide integrated discovery) system, and dimerize the respective monomers through rational design. These dimeric macrocycles specifically and strongly activate Met signalling pathways through receptor dimerization and induce various HGF-like cellular responses, such as branching morphogenesis, in human cells. This work suggests our approach for generating dimeric macrocycles as non-protein ligands for cell surface receptors can be useful for developing potential therapeutics with a broad range of potential applications.

Background: Pleomorphic carcinoma of the lung is a malignant epithelial tumor that contains carcinomatous and sarcomatoid components. Due to its rarity, few studies have been reported, and its clinical and pathological characteristics remain unclear.Method: We retrospectively investigated 22 cases of pleomorphic carcinoma of the lung.Results: Fifteen cases were diagnosed by surgical resection, four by autopsy, and three by transbronchial biopsy. Nineteen patients were male and three were female, and their mean age at diagnosis was 68.3 years (± 10.1).Eighteen were current-or ex-smokers with substantial smoking histories (mean 46.4 pack-years). Sixteen patients had symptoms: hemoptysis and cough were commonly seen. Chest computed tomography (CT) findings revealed that the tumors were quite large (mean diameter 45.3 ± 21.9 mm; range 14-110 mm), and 21 tumors were peripherally located. Positron emission tomography with 18-fluorodeoxy-glucose (FDG-PET) was performed in 12 patients, and the Standardized Uptake Value (SUV) tended to be high (9.44 ± 4.98). In the 15 patients who underwent surgical resection, recurrence was common; systemic metastases were also frequently found. Patients who had received surgical 3 treatment with proper follow-up care survived longer than those who did not undergo surgery. Responses to chemotherapy were generally poor, although one patient exhibited partial response to gefitinib.Conclusions: Pulmonary pleomorphic carcinoma has strong malignant potential with frequent distant metastases, as has already been reported. However, this study demonstrated that surgical treatment and appropriate follow-up therapy might result in better prognoses.

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