A large-scale analysis of mRNA polyadenylation of human and mouse genes

By Bin Tian, Jun Hu, Haibo Zhang, C. Lutz. Nucleic Acids Research, 2005

945 citations recorded by the source corpus.

mRNA polyadenylation is a critical cellular process in eukaryotes. It involves 3′ end cleavage of nascent mRNAs and addition of the poly(A) tail, which plays important roles in many aspects of the cellular metabolism of mRNA. The process is controlled by various cis-acting elements surrounding the cleavage site, and their binding factors. In this study, we surveyed genome regions containing cleavage sites [herein called poly(A) sites], for 13 942 human and 11 155 mouse genes. We found that a great proportion of human and mouse genes have alternative polyadenylation (∼54 and 32%, respectively). The conservation of alternative polyadenylation type or polyadenylation configuration between human and mouse orthologs is statistically significant, indicating that alternative polyadenylation is widely employed by these two species to produce alternative gene transcripts. Genes belonging to several functional groups, indicated by their Gene Ontology annotations, are biased with respect to polyadenylation configuration. Many poly(A) sites harbor multiple cleavage sites (51.25% human and 46.97% mouse sites), leading to heterogeneous 3′ end formation for transcripts. This implies that the cleavage process of polyadenylation is largely imprecise. Different types of poly(A) sites, with regard to their relative locations in a gene, are found to have distinct nucleotide composition in surrounding genomic regions. This large-scale study provides important insights into the mechanism of polyadenylation in mammalian species and represents a genomic view of the regulation of gene expression by alternative polyadenylation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f706cc49150490bf6ac3a99750c662cc54206c60

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Citations in the corpus

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.”
Evolution and functions of long noncoding RNAs. (2009, background): “Moreover, about half of human or mouse genes exhibit alternative polyadenylation among their transcripts (Tian et al., 2005).”
QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences (2006, background): “More than half of human genes are known to have alternative polyadenylation (31).”
Mechanisms and consequences of alternative polyadenylation (2011, neutral): “The brain produces two BDNF transcripts encoding the same protein, with either a short or a long 30 UTR (Timmusk et al., 1993).”
Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and Near Stop Codons (2012, neutral): “However, PASs exhibit considerable sequence heterogeneity beyond the canonical AAUAAA consensus (Tian et al., 2005).”
A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation (2015, background): “(2) Recent attention has focused on the exons that, in any particular mRNA, all encode the sameC-terminal amino acids but contain within their 3′ UTRs APA sites that lead to longer or shorter 3′ UTR sequences (Tian et al. 2005; Ji et al. 2009; Darnell 2013).”
Widespread shortening of 3′UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells (2009, neutral): “Although a strong polyadenylation signal usually is located at the 30 end of the 30UTR, nearly all genes have additional polyadenylation signals in their 30UTRs, with about half of human genes possessing conserved APA signals with usage supported by expressed sequence tags (ESTs) (Tian et al., 2005)”
Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development (2009, background): “Over half of mammalian genes contain multiple polyadenylation sites, or poly(A) sites, that lead to transcript variants with different 3 UTRs or coding regions (11).”
Predicting effective microRNA target sites in mammalian mRNAs (2015, methodology): “Previous studies of miRNA targeting have relied on 3 ′ -UTR annotations from databases such as RefSeq, without accounting for abundant alternative 3 ′ -UTR isoforms present in the tissue or cell line of interest ( Tian et al., 2005 ).”