Patterns of variant polyadenylation signal usage in human genes.

By Emmanuel Beaudoing, Susan M. Freier, J. R. Wyatt, Jean-Michel Claverie, D. Gautheret. Genome Research, 2000

700 citations recorded by the source corpus.

The formation of mature mRNAs in vertebrates involves the cleavage and polyadenylation of the pre-mRNA, 10-30 nt downstream of an AAUAAA or AUUAAA signal sequence. The extensive cDNA data now available shows that these hexamers are not strictly conserved. In order to identify variant polyadenylation signals on a large scale, we compared over 8700 human 3' untranslated sequences to 157,775 polyadenylated expressed sequence tags (ESTs), used as markers of actual mRNA 3' ends. About 5600 EST-supported putative mRNA 3' ends were collected and analyzed for significant hexameric sequences. Known polyadenylation signals were found in only 73% of the 3' fragments. Ten single-base variants of the AAUAAA sequence were identified with a highly significant occurrence rate, potentially representing 14.9% of the actual polyadenylation signals. Of the mRNAs, 28.6% displayed two or more polyadenylation sites. In these mRNAs, the poly(A) sites proximal to the coding sequence tend to use variant signals more often, while the 3'-most site tends to use a canonical signal. The average number of ESTs associated with each signal type suggests that variant signals (including the common AUUAAA) are processed less efficiently than the canonical signal and could therefore be selected for regulatory purposes. However, the position of the site in the untranslated region may also play a role in polyadenylation rate.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7a3f720eed7fafbd8dae185046799a3e7aefaea7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Mechanisms and consequences of alternative polyadenylation (2011, unknown): “In these cases, the variant sites are usually located promoter proximal, whereas canonical poly(A) signal often appears downstream of variant sites (Beaudoing et al., 2000).”
A genomic view of alternative splicing (2002, background): “For example, bioinformatics studies have reported that about 25% of genes have alternative polyadenylation forms, that is, mRNAs that are cleaved and polyadenylated at different site”
A large-scale analysis of mRNA polyadenylation of human and mouse genes (2005, methodology): “It has been reported that over 29% of human genes have more than one polyadenylation site (16).”
Interplay between splicing and transcriptional pausing exerts genome-wide control over alternative polyadenylation (2021, background): “These AAGAAA-based PAS did not increase Pol II pausing by themselves (Figure 2) but appeared to be activated by distant TRSM in our mutants.”
RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. (2005, unknown): “In this conext, it is noteworthy that a substantial number of seuenced human cDNAs have poly(A) tails at locations hat lack the signature upstream AAUAAA sequence or lose variants (see, for example, Beaudoing et al. 2000]).”
A quantitative atlas of polyadenylation in five mammals (2012, background): “Cases where the entire read aligned perfectly were considered potential internal priming events, excluding sites with an AAUAAA motif or its variants (Beaudoing et al. 2000) at 40 to 10 nt and/or sites overlapping a 39 end of a RefSeq transcript or EST (610 bases from the end).”
Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms (2008, background): “The observed 47% alternative polyadenylation is much higher than the 29% estimated previously based on EST sequences (14).”
Fast-Find: A novel computational approach to analyzing combinatorial motifs (2006, background): “These restrictions minimize potential concerns about multi-gene families and avoid artifacts from contaminants in the EST libraries [23].”