Animal mitochondrial translation systems contain two serine tRNAs, corresponding to the codons AGY (Y ؍ U and C) and UCN (N ؍ U, C, A, and G), each possessing an unusual secondary structure; tRNA GCU Ser (for AGY) lacks the entire D arm, whereas tRNA UGA Ser (for UCN) has an unusual cloverleaf configuration. We previously demonstrated that a single bovine mitochondrial seryltRNA synthetase (mt SerRS) recognizes these topologically distinct isoacceptors having no common sequence or structure. Recombinant mt SerRS clearly footprinted at the T⌿C loop of each isoacceptor, and kinetic studies revealed that mt SerRS specifically recognized the T⌿C loop sequence in each isoacceptor. However, in the case of tRNA UGA Ser , T⌿C loop-D loop interaction was further required for recognition, suggesting that mt SerRS recognizes the two substrates by distinct mechanisms. mt SerRS could slightly but significantly misacylate mitochondrial tRNA Gln , which has the same T⌿C loop sequence as tRNA UGA Ser , implying that the fidelity of mitochondrial translation is maintained by kinetic discrimination of tRNAs in the network of aminoacyltRNA synthetases.
The promyelocytic leukemia (PML) tumor suppressor protein accumulates in PML nuclear bodies (PML‐NBs), and can induce growth arrest, cellular senescence and apoptosis. PML has also been localized in the cytoplasm, although its function in this localization remains elusive. A general property of primary cancers is their high glycolytic rate which results from increased glucose consumption. However, the mechanism by which cancer cells up‐regulate glycolysis is not well understood. Here, we have shown that cytoplasmic PML (cPML) directly interacts with M2‐type pyruvate kinase (PKM2), a key regulator of carbon fate. PKM2 determines the proportion of carbons derived from glucose that are used for glycolytic energy production. Over‐expression of PML‐2KA mutant in the cytoplasm, which was generated by mutagenesis of the nuclear localization signals of PML, in MCF‐7 breast cancer cells suppressed PKM2 activity and the accumulation of lactate. PKM2 exists in either an active tetrameric form which has high affinity for its substrate phosphoenolpyruvate (PEP) or a less active dimeric form which has low affinity for its substrate. Over‐expression of PML‐2KA suppressed the activity of the tetrameric form of PKM2, but not the dimeric form. Our findings suggest that cPML plays a role in tumor metabolism through its interaction with PKM2.
Animal mitochondrial protein synthesis systems contain two serine tRNAs (tRNAs Ser ) corresponding to the codons AGY and UCN, each possessing an unusual secondary structure; the former lacks the entire D arm, and the latter has a slightly different cloverleaf structure. To elucidate whether these two tRNAs Ser can be recognized by the single animal mitochondrial seryl-tRNA synthetase (mt SerRS), we purified mt SerRS from bovine liver 2400-fold and showed that it can aminoacylate both of them. Specific interaction between mt SerRS and either of the tRNAs Ser was also observed in a gel retardation assay. cDNA cloning of bovine mt SerRS revealed that the deduced amino acid sequence of the enzyme contains 518 amino acid residues. The cDNAs of human and mouse mt SerRS were obtained by reverse transcription-polymerase chain reaction and expressed sequence tag data base searches. Elaborate inspection of primary sequences of mammalian mt SerRSs revealed diversity in the N-terminal domain responsible for tRNA recognition, indicating that the recognition mechanism of mammalian mt SerRS differs considerably from that of its prokaryotic counterpart. In addition, the human mt SerRS gene was found to be located on chromosome 19q13.1, to which the autosomal deafness locus DFNA4 is mapped.
Light transport simulation in rendering is formulated as a numerical integration problem in each pixel, which is commonly estimated by Monte Carlo integration. Monte Carlo integration approximates an integral of a black‐box function by taking the average of many evaluations (i.e. samples) of the function (integrand). For N queries of the integrand, Monte Carlo integration achieves the estimation error of O(1/N). Recently, Johnston [Joh16] introduced quantum super‐sampling (QSS) into rendering as a numerical integration method that can run on quantum computers. QSS breaks the fundamental limitation of the O(1/N) convergence rate of Monte Carlo integration and achieves the faster convergence rate of approximately O(1/N) which is the best possible bound of any quantum algorithms we know today [NW99]. We introduce yet another quantum numerical integration algorithm, quantum coin (QCoin) [AW99], and provide numerical experiments that are unprecedented in the fields of both quantum computing and rendering. We show that QCoin's convergence rate is equivalent to QSS's. We additionally show that QCoin is fundamentally more robust under the presence of noise in actual quantum computers due to its simpler quantum circuit and the use of fewer qubits. Considering various aspects of quantum computers, we discuss how QCoin can be a more practical alternative to QSS if we were to run light transport simulation in quantum computers in the future.
The mitochondrial seryl-tRNA synthetase (mt SerRS) from Bos taurus was overexpressed in Escherichia coli and crystallized using the sitting-drop vapour-diffusion method. Crystals grew in a very narrow range of conditions using PEG 8000 as precipitant at room temperature. An appropriate concentration of lithium sulfate was critical for crystal nucleation. Crystals diffracted well beyond a resolution of 1.6 A and were found to belong to the orthorhombic space group C222(1), with unit-cell parameters a = 79.89, b = 230.42, c = 135.60 A. There is one dimer (M(r) approximately 113 kDa) in the asymmetric unit, with a solvent content of 55%. Efforts to solve the phase problem by molecular replacement are under way.
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