William Lanier

Publications of William Lanier

• Adenosine deamination in human transcripts generates novel microRNA binding sites.

  Authors: Glen M Borchert, Brian L Gilmore, Ryan M Spengler, Yi Xing, William Lanier, Debashish Bhattacharya, Beverly L Davidson

  Human molecular genetics. 09/2009;

  Animals regulate gene expression at multiple levels, contributing to the complexity of the proteome. Among these regulatory events are post-transcriptional gene silencing, mediated by small noncodingAnimals regulate gene expression at multiple levels, contributing to the complexity of the proteome. Among these regulatory events are post-transcriptional gene silencing, mediated by small noncoding RNAs (e.g., microRNAs), and adenosine-to-inosine (A-to-I) editing, generated by adenosine deaminases that act on double stranded RNA (ADAR). Recent data suggest that these regulatory processes are connected at a fundamental level. A-to-I editing can affect Drosha processing or directly alter the microRNA (miRNA) sequences responsible for mRNA targeting. Here, we analyzed the previously reported adenosine deaminations occurring in human cDNAs, and asked if there was a relationship between A-to-I editing events in the mRNA 3' untranslated regions (UTRs) and mRNA::miRNA binding. We find significant correlations between A-to-I editing and changes in miRNA complementarities. In all, over 3,000 of the 12,723 distinct adenosine deaminations assessed were found to form 7-mer complementarities (known as seed matches) to a subset of human miRNAs. In 200 of the ESTs, we also noted editing within a specific 13 nucleotide motif. Strikingly, deamination of this motif simultaneously creates seed matches to three (otherwise unrelated) miRNAs. Our results suggest the creation of miRNA regulatory sites as a novel function for ADAR activity. Consequently, many miRNA target sites may only be identifiable through examining expressed sequences.

• Green evolution and dynamic adaptations revealed by genomes of the marine picoeukaryotes Micromonas.

  Authors: Alexandra Z Worden, Jae-Hyeok Lee, Thomas Mock, Pierre Rouzé, Melinda P Simmons, Andrea L Aerts, Andrew E Allen, Marie L Cuvelier, Evelyne Derelle, Meredith V Everett [......] Jeremy Schmutz, Eve Toulza, Tania Wyss, Alexander Zelensky, Kemin Zhou, E Virginia Armbrust, Debashish Bhattacharya, Ursula W. Goodenough, Yves Van de Peer, Igor V Grigoriev

  Science (New York, N.Y.). 05/2009; 324(5924):268-72.

  Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging fromPicoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.

• Refining Perioperative Glucose Management in Patients Experiencing, or at Risk for, Ischemic Brain Injury.

  Authors: William Lanier, Jeffrey Pasternak

  Anesthesiology. 03/2009;

• Effect of Nitrous Oxide Use on Long-term Neurologic and Neuropsychological Outcome in Patients Who Received Temporary Proximal Artery Occlusion during Cerebral Aneurysm Clipping Surgery.

  Authors: Jeffrey Pasternak, Diana McGregor, William Lanier, Darrell Schroeder, Deborah Rusy, Bradley Hindman, William Clarke, James Torner, Michael Todd

  Anesthesiology. 03/2009;

  BACKGROUND:: The authors explored the relationship between nitrous oxide use and neurologic and neuropsychological outcome in a population of patients likely to experience intraoperative cerebralBACKGROUND:: The authors explored the relationship between nitrous oxide use and neurologic and neuropsychological outcome in a population of patients likely to experience intraoperative cerebral ischemia: those who had temporary cerebral arterial occlusion during aneurysm clipping surgery. METHODS:: A post hoc analysis of a subset of the data from the Intraoperative Hypothermia for Aneurysm Surgery Trial was conducted. Only subjects who had temporary arterial occlusion during surgery were included in the analysis. Metrics of short-term and long-term (i.e., 3 months after surgery) outcome were evaluated via both univariate and multivariate logistic regression analysis. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. RESULTS:: The authors evaluated 441 patients, of which 199 received nitrous oxide. Patients receiving nitrous oxide had a greater risk of delayed ischemic neurologic deficits (i.e., the clinical manifestation of vasospasm) (OR, 1.78, 95% confidence interval[CI], 1.08-2.95; P = 0.025). However, at 3 months after surgery, there was no difference in any metric of gross neurologic outcome: Glasgow Outcome Score (OR, 0.67; CI, 0.44-1.03; P = 0.065), Rankin Score (OR, 0.74; CI, 0.47-1.16; P = 0.192), National Institutes of Health Stroke Scale (OR, 1.02; CI, 0.66-1.56; P = 0.937), or Barthel Index (OR, 0.69; CI, 0.38-1.25; P = 0.22). The risk of impairment on at least one test of neuropsychological function was reduced in those who received nitrous oxide (OR, 0.56; CI, 0.36-0.89; P = 0.013). CONCLUSION:: In this patient population, use of nitrous oxide was associated with an increased risk for the development of delayed ischemic neurologic deficits; however, there was no evidence of detriment to long-term gross neurologic or neuropsychological outcome.

• EST analysis of Ostreococcus lucimarinus, the most compact eukaryotic genome, shows an excess of introns in highly expressed genes.

  Authors: William Lanier, Ahmed Moustafa, Debashish Bhattacharya, Josep M Comeron

  PLoS ONE. 01/2008; 3(5):e2171.

  BACKGROUND: The genome of the pico-eukaryotic (bacterial-sized) prasinophyte green alga Ostreococcus lucimarinus has one of the highest gene densities known in eukaryotes, yet it contains manyBACKGROUND: The genome of the pico-eukaryotic (bacterial-sized) prasinophyte green alga Ostreococcus lucimarinus has one of the highest gene densities known in eukaryotes, yet it contains many introns. Phylogenetic studies suggest this unusually compact genome (13.2 Mb) is an evolutionarily derived state among prasinophytes. The presence of introns in the highly reduced O. lucimarinus genome appears to be in opposition to simple explanations of genome evolution based on unidirectional tendencies, either neutral or selective. Therefore, patterns of intron retention in this species can potentially provide insights into the forces governing intron evolution. METHODOLOGY/PRINCIPAL FINDINGS: Here we studied intron features and levels of expression in O. lucimarinus using expressed sequence tags (ESTs) to annotate the current genome assembly. ESTs were assembled into unigene clusters that were mapped back to the O. lucimarinus Build 2.0 assembly using BLAST and the level of gene expression was inferred from the number of ESTs in each cluster. We find a positive correlation between expression levels and both intron number (R = +0.0893, p = <0.0005) and intron density (number of introns/kb of CDS; R = +0.0753, p = <0.005). CONCLUSIONS/SIGNIFICANCE: In a species with a genome that has been recently subjected to a great reduction of non-coding DNA, these results imply the existence of selective/functional roles for introns that are principally detectable in highly expressed genes. In these cases, introns are likely maintained by balancing the selective forces favoring their maintenance with other mutational and/or selective forces acting on genome size.

• RNA polymerase III transcribes human microRNAs.

  Authors: Glen M Borchert, William Lanier, Beverly L Davidson

  Nature structural & molecular biology. 01/2007; 13(12):1097-101.

  Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomicPrior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.

• Incidence and severity of neovascularization in oxygen- and metabolic acidosis-induced retinopathy depend on rat source.

  Authors: Anna Kitzmann, David Leske, Yi Chen, Andrea Kendall, William Lanier, Jonathan Holmes

  Current eye research. 11/2002; 25(4):215-20.

  PURPOSE: We have previously described oxygen-induced retinopathy (OIR) and metabolic acidosis-induced retinopathy (MAIR) in the neonatal rat, both of which are analogous to human retinopathy ofPURPOSE: We have previously described oxygen-induced retinopathy (OIR) and metabolic acidosis-induced retinopathy (MAIR) in the neonatal rat, both of which are analogous to human retinopathy of prematurity (ROP). Given that rats of identical strain from two commercial suppliers are phenotypically different, we investigated the incidence and severity of preretinal neovascularization (NV) in rats from different suppliers using the OIR and MAIR models. METHODS: Using our established models for OIR and MAIR, 400 newborn Sprague-Dawley rats, obtained from Harlan Laboratories (HSD) and Charles River Laboratories (CRSD), were raised in 16 expanded litters of 25 (6 OIR and 10 MAIR). Beginning at day 1 of life, OIR litters (3 HSD, 3 CRSD) were exposed to 7 daily cycles of hyperoxia (80% O(2), 20.5 hours) and hypoxia (10% O(2), 0.5 hours) with a gradual return to 80% O(2) over 3 hours. OIR rats were sacrificed after 5 days of room air recovery. MAIR litters (5 HSD, 5 CRSD) were raised in room air and gavaged twice daily with NH(4)Cl (10 mM/kg body weight) from day 2 through day 4. MAIR rats were sacrificed after 3 days of recovery. For both OIR and MAIR litters, retinae from left eyes were dissected, ADPase-stained, and flatmounted. Presence and severity of NV was scored and retinal vascular areas measured by a masked observer. RESULTS: In OIR rats, the incidence of NV was higher in CRSD rats than HSD rats (73% vs. 45%, p = 0.002). NV was more severe in CRSD rats than HSD rats (median clock hours 2 vs. 0, p = 0.0001). In MAIR rats, the incidence of NV was comparable between CRSD and HSD rats (29% vs. 34%, p = 0.53) and there was no significant difference in the severity of NV. CONCLUSIONS: Sprague-Dawley rats obtained from two independent commercial sources differed in their incidence and severity of NV associated with OIR, but not with MAIR. Future genetic studies are warranted to investigate the differences between CRSD and HSD rats, which might yield further clues into the pathogenesis of ROP.