FAST DB: a website resource for the study of the expression regulation of human gene products

Human genes use various mechanisms to generate different transcripts having different exon content, which in turn generate multiple protein isoforms having differential and even opposite biological activities. To understand the biological consequences of gene transcriptional activity modulation, it is necessary to integrate the capability of genes to generate distinct functional products, particularly because transcriptional stimuli also affect the exon content of their target gene products. For this purpose, we have developed a bioinformatics suite, FAST DB, which defines easily and accurately the exon content of all known transcripts produced by human genes. In addition, several tools have been developed, including a graphical presentation of all gene products, a sequence multi-alignment of all gene transcripts and an in silico PCR computer program. The FAST DB interface also offers extensive links to website resources for promoter analysis and transcription factor binding site prediction, splicing regulatory sequence prediction, as well as 5′- and 3′-untranslated region analysis. FAST DB has been designed to facilitate studies that integrate transcriptional and post-transcriptional events to investigate the expression regulation of human gene products.

[1]  Xin Chen,et al.  TRANSFAC: an integrated system for gene expression regulation , 2000, Nucleic Acids Res..

[2]  S. Stamm,et al.  Function of Alternative Splicing , 2004 .

[3]  Michael Gribskov,et al.  A Database Designed to Computationally Aid an Experimental Approach to Alternative Splicing , 2003, Pacific Symposium on Biocomputing.

[4]  Michael Recce,et al.  PolyA_DB: a database for mammalian mRNA polyadenylation , 2004, Nucleic Acids Res..

[5]  A. Vinogradov Compactness of human housekeeping genes: selection for economy or genomic design? , 2004, Trends in genetics : TIG.

[6]  Jorng-Tzong Horng,et al.  ProSplicer: a database of putative alternative splicing information derived from protein, mRNA and expressed sequence tag sequence data , 2003, Genome Biology.

[7]  Thangavel Alphonse Thanaraj,et al.  ASD: the Alternative Splicing Database , 2004, Nucleic Acids Res..

[8]  Jane Y. Wu,et al.  Alternative pre-mRNA splicing and regulation of programmed cell death. , 2003, Progress in molecular and subcellular biology.

[9]  Gil Ast,et al.  How did alternative splicing evolve? , 2004, Nature Reviews Genetics.

[10]  Jack E. Tabaska,et al.  Detection of polyadenylation signals in human DNA sequences. , 1999, Gene.

[11]  Takashi Ito,et al.  SKIP modifies gene expression by affecting both transcription and splicing. , 2004, Biochemical and biophysical research communications.

[12]  Gene W. Yeo,et al.  Variation in sequence and organization of splicing regulatory elements in vertebrate genes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. Shamir,et al.  How prevalent is functional alternative splicing in the human genome? , 2004, Trends in genetics : TIG.

[14]  Christopher J. Lee,et al.  Multiple sequence alignment using partial order graphs , 2002, Bioinform..

[15]  D Gautheret,et al.  Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data. , 2001, Genome research.

[16]  Terrence S. Furey,et al.  The DNA sequence and biology of human chromosome 19 , 2004, Nature.

[17]  Qiang Wu,et al.  Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. , 2003, Genome research.

[18]  Bert W O'Malley,et al.  Coordinate Regulation of Transcription and Splicing by Steroid Receptor Coregulators , 2002, Science.

[19]  G. Stephanopoulos,et al.  A compendium of gene expression in normal human tissues. , 2001, Physiological genomics.

[20]  Daniel Gautheret,et al.  The ERPIN server: an interface to profile-based RNA motif identification , 2004, Nucleic Acids Res..

[21]  Niels Grabe,et al.  AliBaba2: Context specific identification of transcription factor binding sites , 2000, Silico Biol..

[22]  Gene W. Yeo,et al.  Variation in alternative splicing across human tissues , 2004, Genome Biology.

[23]  Simon J. Hubbard,et al.  SiteSeer: visualisation and analysis of transcription factor binding sites in nucleotide sequences , 2003, Nucleic Acids Res..

[24]  R. Zhang,et al.  Improving promoter prediction for the NNPP 2 . 2 algorithm : a case study using Escherichia coli DNA sequences , 2004 .

[25]  Graziano Pesole,et al.  UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs , 2004, Nucleic Acids Res..

[26]  Bosiljka Tasic,et al.  Alternative pre-mRNA splicing and proteome expansion in metazoans , 2002, Nature.

[27]  Heike Pospisil,et al.  EASED: Extended Alternatively Spliced EST Database , 2004, Nucleic Acids Res..

[28]  B. O’Malley,et al.  Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Xiang-Dong Fu,et al.  Profiling alternative splicing on fiber-optic arrays , 2002, Nature Biotechnology.

[30]  B. Frey,et al.  Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. , 2004, Molecular cell.

[31]  A. Krainer,et al.  Pre-mRNA splicing in the new millennium. , 2001, Current opinion in cell biology.

[32]  P. Puigserver,et al.  Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. , 2000, Molecular cell.

[33]  Vladimir B. Bajic,et al.  Dragon Promoter Finder: recognition of vertebrate RNA polymerase II promoters , 2002, Bioinform..

[34]  David Haussler,et al.  Improved splice site detection in Genie , 1997, RECOMB '97.

[35]  B. O’Malley,et al.  CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing , 2004, Molecular and Cellular Biology.

[36]  Christopher J. Lee,et al.  Combining partial order alignment and progressive multiple sequence alignment increases alignment speed and scalability to very large alignment problems , 2004, Bioinform..

[37]  B. Blencowe,et al.  Transcriptional Activators Control Splicing and 3′-End Cleavage Levels* , 2003, Journal of Biological Chemistry.

[38]  Jinhua Wang,et al.  ESEfinder: a web resource to identify exonic splicing enhancers , 2003, Nucleic Acids Res..

[39]  A. Kornblihtt,et al.  Transcriptional Activators Differ in Their Abilities to Control Alternative Splicing* , 2002, The Journal of Biological Chemistry.

[40]  Dixie L Mager,et al.  Complex controls: the role of alternative promoters in mammalian genomes. , 2003, Trends in genetics : TIG.

[41]  Martin Vingron,et al.  Increase of functional diversity by alternative splicing. , 2003, Trends in genetics : TIG.

[42]  J. Valcárcel,et al.  Alternative pre-mRNA splicing: the logic of combinatorial control. , 2000, Trends in biochemical sciences.

[43]  A. Kornblihtt,et al.  Promoter Architecture Modulates CFTR Exon 9 Skipping* , 2003, The Journal of Biological Chemistry.

[44]  Bin Tian,et al.  A large-scale analysis of mRNA polyadenylation of human and mouse genes , 2005, Nucleic acids research.

[45]  Jorng-Tzong Horng,et al.  SpliceInfo: an information repository for mRNA alternative splicing in human genome , 2004, Nucleic Acids Res..

[46]  S. Salzberg,et al.  GeneSplicer: a new computational method for splice site prediction. , 2001, Nucleic acids research.

[47]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[48]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[49]  J. Warrington,et al.  Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes. , 2000, Physiological genomics.

[50]  D. S. Prestridge Predicting Pol II promoter sequences using transcription factor binding sites. , 1995, Journal of molecular biology.

[51]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[52]  Christopher B. Burge,et al.  RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons , 2004, Nucleic Acids Res..

[53]  V. Beneš,et al.  Alternative Splicing Microarrays Reveal Functional Expression of Neuron-specific Regulators in Hodgkin Lymphoma Cells* , 2005, Journal of Biological Chemistry.

[54]  Chris M. Brown,et al.  Transterm: a database of mRNAs and translational control elements , 2002, Nucleic Acids Res..

[55]  Yi Xing,et al.  ASAP: the Alternative Splicing Annotation Project , 2003, Nucleic Acids Res..

[56]  S. Burden,et al.  Sequence analysis Improving promoter prediction for the NNPP 2 . 2 algorithm : a case study using Escherichia coli DNA sequences , 2005 .

[57]  P Cramer,et al.  Functional association between promoter structure and transcript alternative splicing. , 1997, Proceedings of the National Academy of Sciences of the United States of America.