Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the covalent link of amino acids to their cognate tRNAs. The selectivity and species-specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital role in maintaining the fidelity of protein synthesis. We report here the first crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with tRNATrp and Trp which, together with biochemical data, reveals the molecular basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the tRNA acceptor arm from the major groove; however, the 3′ end CCA of the tRNA makes a sharp turn to bind at the active site with a deformed conformation. The discriminator base A73 is specifically recognized by an α-helix of the unique N-terminal domain and the anticodon loop by an α-helix insertion of the C-terminal domain. The N-terminal domain appears to be involved in Trp activation, but not essential for tRNA binding and acylation. Structural and sequence comparisons suggest that this novel tRNA binding and recognition mechanism is very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial TrpRSs. Our findings provide insights into the molecular basis of tRNA specificity and species-specificity.

Anillin (ANLN), an actin-binding protein, is required for cytokinesis. Recently, ANLN has been identified as a biomarker in diverse human cancers; however, the precise role of ANLN in breast cancer remains unclear. In this study, we firstly detected the expression of ANLN in 71 patients with breast cancer by immunohistochemistry, and found ANLN was highly expressed in breast cancer tissues. To evaluate the function of ANLN in breast cancer cells, we employed lentivirus-mediated RNA interference to knock down ANLN expression in two human breast cancer cell lines, MDA-MB-231, and ZR-75-30. Knockdown of ANLN remarkably inhibited the proliferation rate and colony formation ability of both breast cancer cell lines. Moreover, flow cytometry analysis showed that depletion of ANLN in MDA-MB-231 cells blocked the cell cycle progression, with more cells delayed at G2/M phase, due to phosphorylation of Cdc2 and suppression of Cyclin D1. Furthermore, knockdown of ANLN strongly suppressed the migration of breast cancer cells, strengthening the evidence that ANLN could be involved in breast cancer progression. Our results may suggest ANLN as a potential target candidate in breast cancer.

Telomeres are eukaryotic protein-DNA complexes found at the ends of linear chromosomes that are essential for maintaining genome integrity and are implicated in cellular aging and cancer. The guanine (G)-rich strand of telomeric DNA, usually elongated by the telomerase reverse transcriptase, can form a higher-order structure known as a G-quadruplex in vitro and in vivo. Several factors that promote or resolve G-quadruplexes have been identified, but the functional importance of these structures for telomere maintenance is not well understood. Here we show that the yeast telomerase subunit Est1p, known to be involved in telomerase recruitment to telomeres, can convert single-stranded telomeric G-rich DNA into a G-quadruplex structure in vitro in a Mg(2+)-dependent manner. Cells carrying Est1p mutants deficient in G-quadruplex formation in vitro showed gradual telomere shortening and cellular senescence, indicating a positive regulatory role for G-quadruplex in the maintenance of telomere length.