PACdb: PolyA Cleavage Site and 3′-UTR Database

Brockman, J. Michael; Singh, Priyam; Liu, Donglin; Quinlan, Sean; Salisbury, Jesse; Graber, Joel H.

doi:10.1093/bioinformatics/bti589

Cited by 51 publications

(55 citation statements)

References 19 publications

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“…The standard approach has been to match transcriptomes to genomes by hybridizing oligo(dT)-primed cDNA from various RNA preparations to genomic microarrays, possible in smaller yeast genomes but still technically challenging for larger mammalian genomes. From these data, many potential mRNA poly(A) sites were assigned (Nam et al 2002;Brockman et al 2005). While a good number corresponded to canonical poly(A) sites as defined by the earlier, above-described mutagenesis experiments, many more potential poly(A) sites were apparently devoid of the expected RNA signals.…”

Section: Polyadenylation Signals and 39 Noncoding Rna (Ncrna) Sequencesmentioning

confidence: 84%

Ending the message: poly(A) signals then and now

Proudfoot¹

2011

Genes Dev.

519

486

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Polyadenylation [poly(A)] signals (PAS) are a defining feature of eukaryotic protein-coding genes. The central sequence motif AAUAAA was identified in the mid1970s and subsequently shown to require flanking, auxiliary elements for both 39-end cleavage and polyadenylation of premessenger RNA (pre-mRNA) as well as to promote downstream transcriptional termination. More recent genomic analysis has established the generality of the PAS for eukaryotic mRNA. Evidence for the mechanism of mRNA 39-end formation is outlined, as is the way this RNA processing reaction communicates with RNA polymerase II to terminate transcription. The widespread phenomenon of alternative poly(A) site usage and how this interrelates with pre-mRNA splicing is then reviewed. This shows that gene expression can be drastically affected by how the message is ended. A central theme of this review is that while genomic analysis provides generality for the importance of PAS selection, detailed mechanistic understanding still requires the direct analysis of specific genes by genetic and biochemical approaches.

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Section: Polyadenylation Signals and 39 Noncoding Rna (Ncrna) Sequencesmentioning

confidence: 84%

Ending the message: poly(A) signals then and now

Proudfoot¹

2011

Genes Dev.

519

486

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“…The prediction tables are based on methodology that improves on earlier EST-based analyses (14)(15)(16)(17)(18)(19) and demonstrates a 97% level of predictive recall on a hand-curated and experimentally supported benchmark transcript set. Exact and comprehensive definition of alternative 3Ј transcript ends will allow for the design of probes that discriminate between alternative forms and thereby support elucidation of the regulatory impact of alternative polyadenylation.…”

Section: Discussionmentioning

confidence: 99%

Identification of gene 3′ ends by automated EST cluster analysis

Muro

Herrington

Janmohamed

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The properties and biology of mRNA transcripts can be affected profoundly by the choice of alternative polyadenylation sites, making definition of the 3 ends of transcripts essential for understanding their regulation. Here we show that 22-52% of sequences in commonly used human and murine ''full-length'' transcript databases may not currently end at bona fide polyadenylation sites. To identify probable transcript termini over the entire murine and human genomes, we analyzed the EST databases for positional clustering of EST ends. The analysis yielded 58,282 murine-and 86,410 human-candidate polyadenylation sites, of which 75% mapped to 23,091 known murine transcripts and 22,891 known human transcripts. The murine dataset correctly predicted 97% of the 3 ends in a manually curated and experimentally supported benchmark transcript set. Of currently known genes, 15% had no associated prediction and 25% had only a single predicted termination site. The remaining genes had an average of 3-4 alternative polyadenylation sites predicted for each murine or human transcript, respectively. The results are made available in the form of tables and an interactive web site that can be mined for rapid assessment of the validity of 3 ends in existing collections, enumeration of potential alternative 3 polyadenylation sites of known transcripts, direct retrieval of terminal sequences for design of probes, and detection of polyadenylation sites not currently mapped to known genes.3Ј UTR ͉ gene prediction ͉ alternative polyadenylation ͉ transcriptome ͉ transcript probe design

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“…The PAS element, optimally manifested as AAUAAA, is conserved throughout metazoans, and to a reduced level in other eukaryotes (Graber et al 1999a,b;Zhao et al 1999;Brockman et al 2005;Lee et al 2007). …”

Section: An Updated Model Of the Sl2 Precursor Mrna Interactionmentioning

confidence: 99%

C. elegans sequences that control trans-splicing and operon pre-mRNA processing

Graber¹,

Salisbury²,

Hutchins³

et al. 2007

RNA

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Many mRNAs in Caenorhabditis elegans are generated through a trans-splicing reaction that adds one of two classes of spliced leader RNA to an independently transcribed pre-mRNA. SL1 leaders are spliced mostly to pre-mRNAs from genes with outrons, intron-like sequences at the 59-ends of the pre-mRNAs. In contrast, SL2 leaders are nearly exclusively trans-spliced to genes that occur downstream in polycistronic pre-mRNAs produced from operons. Operon pre-mRNA processing requires separation into individual transcripts, which is accomplished by 39-processing of upstream genes and spliced leader trans-splicing to the downstream genes. We used a novel computational analysis, based on nonnegative matrix factorization, to identify and characterize significant differences in the cis-acting sequence elements that differentiate various types of functional site, including internal versus terminal 39-processing sites, and SL1 versus SL2 trans-splicing sites. We describe several key elements, including the U-rich (Ur) element that couples 39-processing with SL2 trans-splicing, and a novel outron (Ou) element that occurs upstream of SL1 trans-splicing sites. Finally, we present models of the distinct classes of trans-splicing reaction, including SL1 trans-splicing at the outron, SL2 trans-splicing in standard operons, competitive SL1-SL2 trans-splicing in operons with large intergenic separation, and SL1 trans-splicing in SL1-type operons, which have no intergenic separation.

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PACdb: PolyA Cleavage Site and 3′-UTR Database

Abstract: Available online at http://harlequin.jax.org/pacdb/supplemental.php.

Cited by 51 publications

References 19 publications

Ending the message: poly(A) signals then and now

Ending the message: poly(A) signals then and now

Identification of gene 3′ ends by automated EST cluster analysis

C. elegans sequences that control trans-splicing and operon pre-mRNA processing

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