alternative polyadenylation in human , mouse , and rat Computational analysis of 3 '-ends of ESTs shows four classes of data

Alternative initiation, splicing, and polyadenylation are key mechanisms used by many organisms to generate diversity among mature mRNA transcripts originating from the same transcription unit. While previous computational analyses of alternative polyadenylation have focused on polyadenylation activities within or downstream of the normal 3'-terminal exons, we present the results of the first genome-wide analysis of patterns of alternative polyadenylation in the human, mouse, and rat genomes occurring over the entire transcribed regions of mRNAs using 3'-ESTs with poly(A) tails aligned to genomic sequences. Four distinct classes of patterns of alternative polyadenylation result from this analysis: tandem poly(A) sites, composite exons, hidden exons, and truncated exons. We estimate that at least 49% (human), 31% (mouse), and 28% (rat) of polyadenylated transcription units have alternative polyadenylation. A portion of these alternative polyadenylation events result in new protein isoforms.

[1]  Jing Zhao,et al.  Formation of mRNA 3′ Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis , 1999, Microbiology and Molecular Biology Reviews.

[2]  G. Edwalds-Gilbert,et al.  Alternative poly(A) site selection in complex transcription units: means to an end? , 1997, Nucleic acids research.

[3]  N. Proudfoot,et al.  Multiple Transcript Cleavage Precedes Polymerase Release in Termination by RNA Polymerase II , 2001, Cell.

[4]  G. Rubin,et al.  A computer program for aligning a cDNA sequence with a genomic DNA sequence. , 1998, Genome research.

[5]  J. Qiu,et al.  Alternative Polyadenylation of Adeno-associated Virus Type 5 RNA within an Internal Intron Is Governed by the Distance between the Promoter and the Intron and Is Inhibited by U1 Small Nuclear RNP Binding to the Intervening Donor* , 2004, Journal of Biological Chemistry.

[6]  A. Kornblihtt,et al.  Multiple links between transcription and splicing. , 2004, RNA.

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

[8]  R. Tjian,et al.  Transcription regulation and animal diversity , 2003, Nature.

[9]  C. V. Jongeneel,et al.  Long-range heterogeneity at the 3' ends of human mRNAs. , 2002, Genome research.

[10]  Graziano Pesole,et al.  UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs , 2000, Nucleic Acids Res..

[11]  R. Benavente,et al.  Meiotic lamin C2: the unique amino-terminal hexapeptide GNAEGR is essential for nuclear envelope association. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Marc Dreyfus,et al.  The Poly(A) Tail of mRNAs Bodyguard in Eukaryotes, Scavenger in Bacteria , 2002, Cell.

[13]  A. Furger,et al.  Integrating mRNA Processing with Transcription , 2002, Cell.

[14]  Fred Winston,et al.  Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene , 2004, Nature.

[15]  S. Cawley,et al.  Unbiased Mapping of Transcription Factor Binding Sites along Human Chromosomes 21 and 22 Points to Widespread Regulation of Noncoding RNAs , 2004, Cell.

[16]  S Audic,et al.  Alternate polyadenylation in human mRNAs: a large-scale analysis by EST clustering. , 1998, Genome research.

[17]  L. Clerch,et al.  A region in the 3' UTR of MnSOD RNA enhances translation of a heterologous RNA. , 2000, Biochemical and biophysical research communications.

[18]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[19]  Antonin Morillon,et al.  Expression of Human Fibroblast Growth Factor 2 mRNA Is Post-transcriptionally Controlled by a Unique Destabilizing Element Present in the 3′-Untranslated Region between Alternative Polyadenylation Sites* , 1999, The Journal of Biological Chemistry.

[20]  M. Boguski,et al.  dbEST — database for “expressed sequence tags” , 1993, Nature Genetics.

[21]  D. Gautheret,et al.  Patterns of variant polyadenylation signal usage in human genes. , 2000, Genome research.

[22]  Donna R. Maglott,et al.  RefSeq and LocusLink: NCBI gene-centered resources , 2001, Nucleic Acids Res..

[23]  R. Singer,et al.  Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype , 1994, The Journal of cell biology.