TY - JOUR T1 - Distinct Rap1 activity states control the extent of epithelial invagination via α-catenin. JF - Dev Cell Y1 - 2013 A1 - Wang, Yu-Chiun A1 - Khan, Zia A1 - Wieschaus, Eric F KW - Actins KW - alpha Catenin KW - Animals KW - Cell Adhesion KW - Cell Adhesion Molecules KW - Cell Membrane KW - Cell Shape KW - Drosophila KW - Drosophila Proteins KW - Embryo, Nonmammalian KW - Enzyme Activation KW - Epithelial Cells KW - Genes, Insect KW - Green Fluorescent Proteins KW - GTP Phosphohydrolases KW - GTPase-Activating Proteins KW - Intercellular Junctions KW - RNA Interference KW - Time factors KW - Time-Lapse Imaging AB -

Localized cell shape change initiates epithelial folding, while neighboring cell invagination determines the final depth of an epithelial fold. The mechanism that controls the extent of invagination remains unknown. During Drosophila gastrulation, a higher number of cells undergo invagination to form the deep posterior dorsal fold, whereas far fewer cells become incorporated into the initially very similar anterior dorsal fold. We find that a decrease in α-catenin activity causes the anterior fold to invaginate as extensively as the posterior fold. In contrast, constitutive activation of the small GTPase Rap1 restricts invagination of both dorsal folds in an α-catenin-dependent manner. Rap1 activity appears spatially modulated by Rapgap1, whose expression levels are high in the cells that flank the posterior fold but low in the anterior fold. We propose a model whereby distinct activity states of Rap1 modulate α-catenin-dependent coupling between junctions and actin to control the extent of epithelial invagination.

VL - 25 CP - 3 M3 - 10.1016/j.devcel.2013.04.002 ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny. JF - Nature Y1 - 2007 A1 - Clark, Andrew G A1 - Eisen, Michael B A1 - Smith, Douglas R A1 - Bergman, Casey M A1 - Oliver, Brian A1 - Markow, Therese A A1 - Kaufman, Thomas C A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N A1 - Pollard, Daniel A A1 - Sackton, Timothy B A1 - Larracuente, Amanda M A1 - Singh, Nadia D A1 - Abad, Jose P A1 - Abt, Dawn N A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W A1 - Aquadro, Charles F A1 - Ardell, David H A1 - Arguello, Roman A1 - Artieri, Carlo G A1 - Barbash, Daniel A A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A A1 - Bradley, Robert K A1 - Brand, Adrianne D A1 - Brent, Michael R A1 - Brooks, Angela N A1 - Brown, Randall H A1 - Butlin, Roger K A1 - Caggese, Corrado A1 - Calvi, Brian R A1 - Bernardo de Carvalho, A A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E A1 - Chang, Jean L A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W A1 - Comeron, Josep M A1 - Costello, James C A1 - Coyne, Jerry A A1 - Daub, Jennifer A1 - David, Robert G A1 - Delcher, Arthur L A1 - Delehaunty, Kim A1 - Do, Chuong B A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D A1 - Filipski, Alan A1 - Findeiss, Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C L A1 - Gardiner, Anastasia A1 - Garfield, David A A1 - Garvin, Barry E A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A A1 - Haerty, Wilfried A1 - Hahn, Matthew W A1 - Halligan, Daniel L A1 - Halpern, Aaron L A1 - Halter, Gillian M A1 - Han, Mira V A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S A1 - Holmes, Ian A1 - Hoskins, Roger A A1 - Hubisz, Melissa J A1 - Hultmark, Dan A1 - Huntley, Melanie A A1 - Jaffe, David B A1 - Jagadeeshan, Santosh A1 - Jeck, William R A1 - Johnson, Justin A1 - Jones, Corbin D A1 - Jordan, William C A1 - Karpen, Gary H A1 - Kataoka, Eiko A1 - Keightley, Peter D A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F A1 - Koerich, Leonardo B A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H A1 - Lapoint, Richard A1 - Lazzaro, Brian P A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U A1 - Montooth, Kristi A1 - Mount, Stephen M A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A F A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S A1 - Pesole, Graziano A1 - Phillippy, Adam M A1 - Ponting, Chris P A1 - Pop, Mihai A1 - Porcelli, Damiano A1 - Powell, Jeffrey R A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D A1 - Reed, Laura K A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A A1 - Rieger, Tania T A1 - Ritchie, Michael G A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J A1 - Sato, Hajime A1 - Schaeffer, Stephen W A1 - Schatz, Michael C A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B A1 - Smith, Chris D A1 - Smith, Temple F A1 - Spieth, John A1 - Stage, Deborah E A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M A1 - Valente, Vera L S A1 - Venter, Eli A1 - Venter, J Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G A1 - Vilella, Albert J A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K A1 - Wing, Rod A A1 - Wolfner, Mariana F A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung-I A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - De Haan, Georgius A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain KW - Animals KW - Codon KW - DNA Transposable Elements KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - Gene Order KW - Genes, Insect KW - Genome, Insect KW - Genome, Mitochondrial KW - Genomics KW - Immunity KW - Multigene Family KW - Phylogeny KW - Reproduction KW - RNA, Untranslated KW - sequence alignment KW - Sequence Analysis, DNA KW - Synteny AB -

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

VL - 450 CP - 7167 M3 - 10.1038/nature06341 ER - TY - JOUR T1 - Spliceosomal small nuclear RNA genes in 11 insect genomes. JF - RNA Y1 - 2007 A1 - Mount, Stephen M A1 - Gotea, Valer A1 - Lin, Chiao-Feng A1 - Hernandez, Kristina A1 - Makalowski, Wojciech KW - Animals KW - Base Sequence KW - Bees KW - Computational Biology KW - Diptera KW - Evolution, Molecular KW - Genes, Insect KW - Genome, Insect KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Phylogeny KW - Promoter Regions, Genetic KW - RNA Splicing KW - RNA, Small Nuclear KW - Sequence Analysis, RNA KW - Spliceosomes AB -

The removal of introns from the primary transcripts of protein-coding genes is accomplished by the spliceosome, a large macromolecular complex of which small nuclear RNAs (snRNAs) are crucial components. Following the recent sequencing of the honeybee (Apis mellifera) genome, we used various computational methods, ranging from sequence similarity search to RNA secondary structure prediction, to search for putative snRNA genes (including their promoters) and to examine their pattern of conservation among 11 available insect genomes (A. mellifera, Tribolium castaneum, Bombyx mori, Anopheles gambiae, Aedes aegypti, and six Drosophila species). We identified candidates for all nine spliceosomal snRNA genes in all the analyzed genomes. All the species contain a similar number of snRNA genes, with the exception of A. aegypti, whose genome contains more U1, U2, and U5 genes, and A. mellifera, whose genome contains fewer U2 and U5 genes. We found that snRNA genes are generally more closely related to homologs within the same genus than to those in other genera. Promoter regions for all spliceosomal snRNA genes within each insect species share similar sequence motifs that are likely to correspond to the PSEA (proximal sequence element A), the binding site for snRNA activating protein complex, but these promoter elements vary in sequence among the five insect families surveyed here. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns.

VL - 13 CP - 1 M3 - 10.1261/rna.259207 ER - TY - JOUR T1 - Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping. JF - Development Y1 - 2003 A1 - Nagengast, Alexis A A1 - Stitzinger, Shane M A1 - Tseng, Chin-Hsiu A1 - Mount, Stephen M A1 - Salz, Helen K KW - Alternative Splicing KW - Amino Acid Sequence KW - Animals KW - Animals, Genetically Modified KW - Drosophila melanogaster KW - Drosophila Proteins KW - Exons KW - Female KW - Gene Expression Regulation, Developmental KW - Genes, Insect KW - Homeostasis KW - Male KW - Models, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins KW - Point Mutation KW - Ribonucleoprotein, U1 Small Nuclear KW - Ribonucleoproteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Homology, Amino Acid KW - Sex Differentiation AB -

Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.

VL - 130 CP - 3 ER - TY - JOUR T1 - The genome sequence of Drosophila melanogaster. JF - Science Y1 - 2000 A1 - Adams, M D A1 - Celniker, S E A1 - Holt, R A A1 - Evans, C A A1 - Gocayne, J D A1 - Amanatides, P G A1 - Scherer, S E A1 - Li, P W A1 - Hoskins, R A A1 - Galle, R F A1 - George, R A A1 - Lewis, S E A1 - Richards, S A1 - Ashburner, M A1 - Henderson, S N A1 - Sutton, G G A1 - Wortman, J R A1 - Yandell, M D A1 - Zhang, Q A1 - Chen, L X A1 - Brandon, R C A1 - Rogers, Y H A1 - Blazej, R G A1 - Champe, M A1 - Pfeiffer, B D A1 - Wan, K H A1 - Doyle, C A1 - Baxter, E G A1 - Helt, G A1 - Nelson, C R A1 - Gabor, G L A1 - Abril, J F A1 - Agbayani, A A1 - An, H J A1 - Andrews-Pfannkoch, C A1 - Baldwin, D A1 - Ballew, R M A1 - Basu, A A1 - Baxendale, J A1 - Bayraktaroglu, L A1 - Beasley, E M A1 - Beeson, K Y A1 - Benos, P V A1 - Berman, B P A1 - Bhandari, D A1 - Bolshakov, S A1 - Borkova, D A1 - Botchan, M R A1 - Bouck, J A1 - Brokstein, P A1 - Brottier, P A1 - Burtis, K C A1 - Busam, D A A1 - Butler, H A1 - Cadieu, E A1 - Center, A A1 - Chandra, I A1 - Cherry, J M A1 - Cawley, S A1 - Dahlke, C A1 - Davenport, L B A1 - Davies, P A1 - de Pablos, B A1 - Delcher, A A1 - Deng, Z A1 - Mays, A D A1 - Dew, I A1 - Dietz, S M A1 - Dodson, K A1 - Doup, L E A1 - Downes, M A1 - Dugan-Rocha, S A1 - Dunkov, B C A1 - Dunn, P A1 - Durbin, K J A1 - Evangelista, C C A1 - Ferraz, C A1 - Ferriera, S A1 - Fleischmann, W A1 - Fosler, C A1 - Gabrielian, A E A1 - Garg, N S A1 - Gelbart, W M A1 - Glasser, K A1 - Glodek, A A1 - Gong, F A1 - Gorrell, J H A1 - Gu, Z A1 - Guan, P A1 - Harris, M A1 - Harris, N L A1 - Harvey, D A1 - Heiman, T J A1 - Hernandez, J R A1 - Houck, J A1 - Hostin, D A1 - Houston, K A A1 - Howland, T J A1 - Wei, M H A1 - Ibegwam, C A1 - Jalali, M A1 - Kalush, F A1 - Karpen, G H A1 - Ke, Z A1 - Kennison, J A A1 - Ketchum, K A A1 - Kimmel, B E A1 - Kodira, C D A1 - Kraft, C A1 - Kravitz, S A1 - Kulp, D A1 - Lai, Z A1 - Lasko, P A1 - Lei, Y A1 - Levitsky, A A A1 - Li, J A1 - Li, Z A1 - Liang, Y A1 - Lin, X A1 - Liu, X A1 - Mattei, B A1 - McIntosh, T C A1 - McLeod, M P A1 - McPherson, D A1 - Merkulov, G A1 - Milshina, N V A1 - Mobarry, C A1 - Morris, J A1 - Moshrefi, A A1 - Mount, S M A1 - Moy, M A1 - Murphy, B A1 - Murphy, L A1 - Muzny, D M A1 - Nelson, D L A1 - Nelson, D R A1 - Nelson, K A A1 - Nixon, K A1 - Nusskern, D R A1 - Pacleb, J M A1 - Palazzolo, M A1 - Pittman, G S A1 - Pan, S A1 - Pollard, J A1 - Puri, V A1 - Reese, M G A1 - Reinert, K A1 - Remington, K A1 - Saunders, R D A1 - Scheeler, F A1 - Shen, H A1 - Shue, B C A1 - Sidén-Kiamos, I A1 - Simpson, M A1 - Skupski, M P A1 - Smith, T A1 - Spier, E A1 - Spradling, A C A1 - Stapleton, M A1 - Strong, R A1 - Sun, E A1 - Svirskas, R A1 - Tector, C A1 - Turner, R A1 - Venter, E A1 - Wang, A H A1 - Wang, X A1 - Wang, Z Y A1 - Wassarman, D A A1 - Weinstock, G M A1 - Weissenbach, J A1 - Williams, S M A1 - Worley, K C A1 - Wu, D A1 - Yang, S A1 - Yao, Q A A1 - Ye, J A1 - Yeh, R F A1 - Zaveri, J S A1 - Zhan, M A1 - Zhang, G A1 - Zhao, Q A1 - Zheng, L A1 - Zheng, X H A1 - Zhong, F N A1 - Zhong, W A1 - Zhou, X A1 - Zhu, S A1 - Zhu, X A1 - Smith, H O A1 - Gibbs, R A A1 - Myers, E W A1 - Rubin, G M A1 - Venter, J C KW - Animals KW - Biological Transport KW - Chromatin KW - Cloning, Molecular KW - Computational Biology KW - Contig Mapping KW - Cytochrome P-450 Enzyme System KW - DNA Repair KW - DNA Replication KW - Drosophila melanogaster KW - Euchromatin KW - Gene Library KW - Genes, Insect KW - Genome KW - Heterochromatin KW - Insect Proteins KW - Nuclear Proteins KW - Protein Biosynthesis KW - Sequence Analysis, DNA KW - Transcription, Genetic AB -

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

VL - 287 CP - 5461 ER - TY - JOUR T1 - Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. JF - Mol Cell Biol Y1 - 1995 A1 - Peng, X A1 - Mount, S M KW - Alleles KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - DNA Primers KW - Drosophila melanogaster KW - Drosophila Proteins KW - Frameshift Mutation KW - Genes, Dominant KW - Genes, Insect KW - Molecular Sequence Data KW - Nuclear Proteins KW - Phosphoproteins KW - Point Mutation KW - Protein Structure, Tertiary KW - Proteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Deletion KW - Sex Determination Analysis AB -

SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5' splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo.

VL - 15 CP - 11 ER - TY - JOUR T1 - Localization of sequences required for size-specific splicing of a small Drosophila intron in vitro. JF - J Mol Biol Y1 - 1995 A1 - Guo, M A1 - Mount, S M KW - Animals KW - Base Sequence KW - Cell Line KW - DNA KW - Drosophila KW - Genes, Insect KW - HeLa Cells KW - HUMANS KW - Introns KW - Molecular Sequence Data KW - Myosin Heavy Chains KW - RNA Splicing KW - Species Specificity AB -

Many introns in Drosophila and other invertebrates are less than 80 nucleotides in length, too small to be recognized by the vertebrate splicing machinery. Comparison of nuclear splicing extracts from human HeLa and Drosophila Kc cells has revealed species-specificity, consistent with the observed size differences. Here we present additional results with the 68 nucleotide fifth intron of the Drosophila myosin heavy chain gene. As observed with the 74 nucleotide second intron of the Drosophila white gene, the wild-type myosin intron is accurately spliced in a homologous extract, and increasing the size by 16 nucleotides both eliminates splicing in the Drosophila extract and allows accurate splicing in the human extract. In contrast to previous results, however, an upstream cryptic 5' splice site is activated when the wild-type myosin intron is tested in a human HeLa cell nuclear extract, resulting in the removal of a 98 nucleotide intron. The size dependence of splicing in Drosophila extracts is also intron-specific; we noted that a naturally larger (150 nucleotide) intron from the ftz gene is efficiently spliced in Kc cell extracts that do not splice enlarged introns (of 84, 90, 150 or 350 nucleotides) derived from the 74 nucleotide white intron. Here, we have exploited that observation, using a series of hybrid introns to show that a region of 46 nucleotides at the 3' end of the white intron is sufficient to confer the species-specific size effect. At least two sequence elements within this region, yet distinct from previously described branchpoint and pyrimidine tract signals, are required for efficient splicing of small hybrid introns in vitro.

VL - 253 CP - 3 M3 - 10.1006/jmbi.1995.0564 ER - TY - JOUR T1 - P element-mediated in vivo deletion analysis of white-apricot: deletions between direct repeats are strongly favored. JF - Genetics Y1 - 1994 A1 - Kurkulos, M A1 - Weinberg, J M A1 - Roy, D A1 - Mount, S M KW - Alleles KW - Animals KW - Animals, Genetically Modified KW - Base Sequence KW - Crosses, Genetic KW - DNA KW - DNA Transposable Elements KW - Drosophila KW - Eye Color KW - Female KW - Genes, Insect KW - Male KW - Molecular Sequence Data KW - Nucleotidyltransferases KW - PHENOTYPE KW - Recombination, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Sequence Deletion KW - Transformation, Genetic KW - Transposases AB -

We have isolated and characterized deletions arising within a P transposon, P[hswa], in the presence of P transposase. P[hswa] carries white-apricot (wa) sequences, including a complete copia element, under the control of an hsp70 promoter, and resembles the original wa allele in eye color phenotype. In the presence of P transposase, P[hswa] shows a high overall rate (approximately 3%) of germline mutations that result in increased eye pigmentation. Of 234 derivatives of P[hswa] with greatly increased eye pigmentation, at least 205 carried deletions within copia. Of these, 201 were precise deletions between the directly repeated 276-nucleotide copia long terminal repeats (LTRs), and four were unique deletions. High rates of transposase-induced precise deletion were observed within another P transposon carrying unrelated 599 nucleotide repeats (yeast 2 mu FLP; recombinase target sites) separated by 5.7 kb. Our observation that P element-mediated deletion formation occurs preferentially between direct repeats suggests general methods for controlling deletion formation.

VL - 136 CP - 3 ER -