Sequence Alignment

Publication Title: 

Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans.

Denzel, Martin S.
Storm, Nadia J.
Gutschmidt, Aljona
Baddi, Ruth
Hinze, Yvonne
Jarosch, Ernst
Sommer, Thomas
Hoppe, Thorsten
Antebi, Adam
Publication Title: 
Genes & Development

It is well established that the template for telomeric DNA synthesis is provided by the RNA subunit of telomerase; however, the additional functions provided by most of the rest of the RNA (>1000 nucleotides in budding yeast) are largely unknown. By alignment of telomerase RNAs of Saccharomyces cerevisiae and six Kluyveromyces species followed by mutagenesis of the S. cerevisiae RNA, we found a conserved region that is essential for telomere maintenance.

Seto, Anita G.
Livengood, April J.
Tzfati, Yehuda
Blackburn, Elizabeth H.
Cech, Thomas R.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Telomeric DNA sequences have generally been found to be remarkably conserved in evolution, typically consisting of repeated, very short sequence units containing clusters of G residues. Recently however the telomeric DNA of the asexual yeast Candida albicans was shown to consist of much longer repeat units. Here we report the identification of seven additional telomeric sequences from sexual and asexual budding yeast species.

McEachern, M. J.
Blackburn, E. H.
Publication Title: 

The RNA moiety of the ribonucleoprotein enzyme telomerase contains the template for telomeric DNA synthesis. We present a secondary structure model for telomerase RNA, derived by a phylogenetic comparative analysis of telomerase RNAs from seven tetrahymenine ciliates. The telomerase RNA genes from Tetrahymena malaccensis, T. pyriformis, T. hyperangularis, T. pigmentosa, T. hegewishii, and Glaucoma chattoni were cloned, sequenced, and compared with the previously cloned RNA gene from T. thermophila and with each other.

Romero, D. P.
Blackburn, E. H.
Publication Title: 
Human Molecular Genetics

Sprouty proteins are regulators of cell growth and branching morphogenesis. Unlike mouse Spry3, which is X-linked, human SPRY3 maps to the pseudoautosomal region 2; however, the human Y-linked allele is not expressed due to epigenetic silencing by an unknown mechanism. SPRY3 maps adjacent to X-linked Trimethyllysine hydroxylase epsilon (TMLHE), recently identified as an autism susceptibility gene. We report that Spry3 is highly expressed in central and peripheral nervous system ganglion cells in mouse and human, including cerebellar Purkinje cells and retinal ganglion cells.

Ning, Zhenfei
McLellan, Andrew S.
Ball, Melanie
Wynne, Freda
O'Neill, Cora
Mills, Walter
Quinn, John P.
Kleinjan, Dirk A.
Anney, Richard J.
Carmody, Ruaidhre J.
O'Keeffe, Gerard
Moore, Tom
Publication Title: 
The Journal of Biological Chemistry

Artemisinin and its derivatives are important new antimalarial drugs. When Plasmodium falciparum-infected erythrocytes are incubated with [10-3H]dihydroartemisinin, several malaria-specific proteins become labeled. One of these proteins is the P. falciparum translationally controlled tumor protein (TCTP) homolog. In vitro, dihydroartemisinin reacts covalently with recombinant TCTP in the presence of hemin. The association between drug and protein increases with increasing drug concentration, plateauing at approximately 1 drug/TCTP molecule.

Bhisutthibhan, J.
Pan, X. Q.
Hossler, P. A.
Walker, D. J.
Yowell, C. A.
Carlton, J.
Dame, J. B.
Meshnick, S. R.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis.

Pillai, Dylan R.
Hijar, Gisely
Montoya, Ysabel
Marouiño, Wilmer
Ruebush, Trenton K.
Wongsrichanalai, Chansuda
Kain, Kevin C.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

With >1 million deaths annually, mostly among children in sub-Saharan Africa, malaria poses one of the most critical challenges in medicine today. Although introduction of the artemisinin class of antimalarial drugs has offered a temporary solution to the problem of drug resistance, new antimalarial drugs are needed to ensure effective control of the disease in the future. Herein, we have investigated members of the methionine aminopeptidase family as potential antimalarial targets.

Chen, Xiaochun
Chong, Curtis R.
Shi, Lirong
Yoshimoto, Tadashi
Sullivan, David J.
Liu, Jun O.
Publication Title: 
BMC genomics

BACKGROUND: Glandular trichomes produce a wide variety of commercially important secondary metabolites in many plant species. The most prominent anti-malarial drug artemisinin, a sesquiterpene lactone, is produced in glandular trichomes of Artemisia annua. However, only limited genomic information is currently available in this non-model plant species. RESULTS: We present a global characterization of A. annua glandular trichome transcriptome using 454 pyrosequencing.

Wang, Wei
Wang, Yejun
Zhang, Qing
Qi, Yan
Guo, Dianjing
Publication Title: 
The Journal of Infectious Diseases

BACKGROUND: Amodiaquine (AQ) is paired with artesunate (AS) or sulfadoxine-pyrimethamine (SP) in recommended antimalarial regimens. It is unclear how readily AQ resistance will be selected with combination chemotherapy. METHODS: We collected 61 Plasmodium falciparum samples from a cohort of Ugandan children randomized for treatment with AQ-SP, AS-AQ, or artemether-lumefantrine (AL) for uncomplicated malaria.

Nawaz, Fatima
Nsobya, Samuel L.
Kiggundu, Moses
Joloba, Moses
Rosenthal, Philip J.


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