RESUMEN
Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.
Asunto(s)
Genoma , Ratones/genética , ARN sin Sentido/biosíntesis , Transcripción Genética , Animales , Regulación de la Expresión Génica , Humanos , Interferencia de ARN , ARN Mensajero/biosíntesisRESUMEN
This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
Asunto(s)
Genoma , Ratones/genética , Regiones Terminadoras Genéticas , Sitio de Iniciación de la Transcripción , Transcripción Genética , Regiones no Traducidas 3' , Animales , Secuencia de Bases , Secuencia Conservada , ADN Complementario/química , Genoma Humano , Genómica , Humanos , Regiones Promotoras Genéticas , Proteínas/genética , ARN/química , ARN/clasificación , Empalme del ARN , ARN no Traducido/química , Secuencias Reguladoras de Ácido RibonucleicoRESUMEN
Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
Asunto(s)
ADN Complementario/genética , Genómica , Ratones/genética , Transcripción Genética/genética , Empalme Alternativo/genética , Secuencias de Aminoácidos , Animales , Cromosomas de los Mamíferos/genética , Clonación Molecular , Bases de Datos Genéticas , Etiquetas de Secuencia Expresada , Genes/genética , Genómica/métodos , Humanos , Proteínas de la Membrana/genética , Mapeo Físico de Cromosoma , Estructura Terciaria de Proteína , Proteoma/química , Proteoma/genética , ARN sin Sentido/genética , ARN Mensajero/análisis , ARN Mensajero/genética , ARN no Traducido/análisis , ARN no Traducido/genética , Sitio de Iniciación de la TranscripciónRESUMEN
The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
Asunto(s)
Biología Computacional , ADN Complementario , Ratones/genética , Animales , Mapeo Cromosómico , Enzimas/genética , Biblioteca de Genes , Genoma , Humanos , Ratones Endogámicos C57BL , Biosíntesis de Proteínas , Estructura Terciaria de Proteína , ARN Mensajero , Análisis de Secuencia de ADNRESUMEN
The frequencies of chromosome aberrations, sister chromatid exchanges (SCEs), and cell cycle kinetics were examined in cultured lymphocytes from five patients with hereditary adenomatosis of the colon and rectum (ACR) [three patients with Gardner's syndrome (GS) and two patients with familial polyposis coli (FPC)]. The frequency of numerical chromosome aberrations was no different in metaphase cells at the first and second replication cycles (M1 and M2) in the ACR patients and control subjects. The percentage of structural chromosome aberrations in both M1 and M2 cells was somewhat higher in the ACR patients as compared with the controls. Neither spontaneous nor mitomycin C-induced SCE frequencies in the patients with ACR were different from the controls, except for one patient with GS, who showed a remarkably high spontaneous SCE frequency. This patient is the mother of a son who had hepatoblastoma. The cell replication index (RI) was lower in the GS patients than in the controls. However, the RI in the FPC patients did not differ from that of the controls.
Asunto(s)
Aberraciones Cromosómicas , Neoplasias del Colon/genética , Síndrome de Gardner/genética , Pólipos Intestinales/genética , Neoplasias del Recto/genética , Intercambio de Cromátides Hermanas , Adulto , Ciclo Celular , Femenino , Humanos , Cinética , Linfocitos/ultraestructuraRESUMEN
Measurement analysis of lymphocyte prometaphase chromosomes from three patients with hereditary adenomatosis of the colon and rectum could not confirm the heteromorphism of chromosome #2 homologues, which was suggested by Gardner et al. Instead, the analysis showed to what extent individual homologous pairs are "heteromorphic" quantitatively.
