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91.
Evidence that miRNAs are different from other RNAs 总被引:13,自引:0,他引:13
Zhang BH Pan XP Cox SB Cobb GP Anderson TA 《Cellular and molecular life sciences : CMLS》2006,63(2):246-254
An examination of 513 known pre-miRNAs and 237 other RNAs (tRNA, rRNA, and mRNA) revealed that miRNAs were significantly different
from other RNAs (p < 0.001). miRNA genes were less conserved than other RNA genes, although their mature miRNA sequences were
highly conserved. The A+U content of pre-miRNAs was higher than non-coding RNA (p < 0.001), but lower than mRNAs. The nucleotides
in pre-miRNAs formed more hydrogen bonds and base pairs than in other RNAs. miRNAs had higher negative adjusted minimal folding
free energies than other RNAs except tRNAs (p < 0.001). The MFE index (MFEI) was a sufficient criterion to distinguish miRNAs
from all coding and non-coding RNAs (p < 0.001). The MFEI for miRNAs was 0.97, significantly higher than tRNAs (0.64), rRNAs
(0.59), or mRNAs (0.65). Our findings should facilitate the prediction and identification of new miRNAs using computational
and experimental strategies.
Received 5 October 2005; received after revision 4 November 2005; accepted 16 November 2005 相似文献
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93.
Nicholas AK Khurshid M Désir J Carvalho OP Cox JJ Thornton G Kausar R Ansar M Ahmad W Verloes A Passemard S Misson JP Lindsay S Gergely F Dobyns WB Roberts E Abramowicz M Woods CG 《Nature genetics》2010,42(11):1010-1014
Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain. We identified WDR62 as the second most common cause of MCPH after finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7 proteins. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain. 相似文献
94.
Comparative analysis of zebrafish bone morphogenetic proteins 2, 4 and 16: molecular and evolutionary perspectives 总被引:1,自引:0,他引:1
95.
L R Osborne M Li B Pober D Chitayat J Bodurtha A Mandel T Costa T Grebe S Cox L C Tsui S W Scherer 《Nature genetics》2001,29(3):321-325
Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions. 相似文献
96.
Mima moundfields were investigated at the Lawrence Memorial Grassland Preserve, located on the Columbia Plateau in southern Wasco County, Oregon, and at three locations in the San Luis Valley and Sangre de Cristo Mountains, southern Colorado, to test the alternative hypotheses of mound origins by erosion, frost action, and soil translocation by geomyid pocket gophers. The concentrations of two size classes of small stones, gravel (8-15 mm diameter) and pebbles (15-50 mm diameter), were sampled along mound-to-intermound transects and at different depths within the mounds. Numbers and masses of small stones per unit soil volume increased from intermounds to mounds tops at the Colorado sites and from mound edge to mound top at the Oregon site, where thin intermound soils lay directly on the weathering surface of basalt bedrock. Numbers and masses of small stones in the surface soil of mound tops were greater than or similar to concentrations in deeper layers. Mean masses of individual pebbles were greater in the intermound zone than in mound soils at the Oregon site, but did not differ along mound-intermound gradient at the Oregon site and at one Colorado site, being highest at mound edges or in intermounds. These observations support the hypothesis that mounds are formed by centripetal translocation of soil by geomyid pocket gophers, and are contrary to predictions based on theories assuming erosion or frost action to be the mechanism of mound formation. 相似文献
97.
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99.
A chain initiation factor common to both modular and aromatic polyketide synthases. 总被引:18,自引:0,他引:18
C Bisang P F Long J Cortés J Westcott J Crosby A L Matharu R J Cox T J Simpson J Staunton P F Leadlay 《Nature》1999,401(6752):502-505
Antibiotic-producing polyketide synthases (PKSs) are enzymes responsible for the biosynthesis in Streptomyces and related filamentous bacteria of a remarkably broad range of bioactive metabolites, including antitumour aromatic compounds such as mithramycin and macrolide antibiotics such as erythromycin. The molecular basis for the selection of the starter unit on aromatic PKSs is unknown. Here we show that a component of aromatic PKS, previously named 'chain-length factor', is a factor required for polyketide chain initiation and that this factor has decarboxylase activity towards malonyl-ACP (acyl carrier protein). We have re-examined the mechanism of initiation on modular PKSs and have identified as a specific initiation factor a domain of previously unknown function named KSQ, which operates like chain-length factor. Both KSQ and chain-length factor are similar to the ketosynthase domains that catalyse polyketide chain extension in modular multifunctional PKSs and in aromatic PKSs, respectively, except that the ketosynthase domain active-site cysteine residue is replaced by a highly conserved glutamine in KSQ and in chain-length factor. The glutamine residue is important both for decarboxylase activity and for polyketide synthesis. 相似文献
100.
Cox JJ Reimann F Nicholas AK Thornton G Roberts E Springell K Karbani G Jafri H Mannan J Raashid Y Al-Gazali L Hamamy H Valente EM Gorman S Williams R McHale DP Wood JN Gribble FM Woods CG 《Nature》2006,444(7121):894-898
The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit. 相似文献