Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation.

Polyadenylation is an essential step for the maturation of almost all cellular mRNAs in eukaryotes. In human cells, most poly(A) sites are flanked by the upstream AAUAAA hexamer or a close variant, and downstream U/GU-rich elements. In yeast and plants, additional cis elements have been found to be located upstream of the poly(A) site, including UGUA, UAUA, and U-rich elements. In this study, we have developed a computer program named PROBE (Polyadenylation-Related Oligonucleotide Bidimensional Enrichment) to identify cis elements that may play regulatory roles in mRNA polyadenylation. By comparing human genomic sequences surrounding frequently used poly(A) sites with those surrounding less frequently used ones, we found that cis elements occurring in yeast and plants also exist in human poly(A) regions, including the upstream U-rich elements, and UAUA and UGUA elements. In addition, several novel elements were found to be associated with human poly(A) sites, including several G-rich elements. Thus, we suggest that many cis elements are evolutionarily conserved among eukaryotes, and human poly(A) sites have an additional set of cis elements that may be involved in the regulation of mRNA polyadenylation.

[1]  K. Venkataraman,et al.  Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition. , 2005, Genes & development.

[2]  Bin Tian,et al.  Alternative polyadenylation of cyclooxygenase-2 , 2005, Nucleic acids research.

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

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

[5]  G. Crooks,et al.  WebLogo: a sequence logo generator. , 2004, Genome research.

[6]  Chunxiao Wu,et al.  Secondary Structure as a Functional Feature in the Downstream Region of Mammalian Polyadenylation Signals , 2004, Molecular and Cellular Biology.

[7]  W. Keller,et al.  Human Fip1 is a subunit of CPSF that binds to U‐rich RNA elements and stimulates poly(A) polymerase , 2004, The EMBO journal.

[8]  J. Graber,et al.  Variations in yeast 3'-processing cis-elements correlate with transcript stability. , 2003, Trends in genetics : TIG.

[9]  Gabriele Varani,et al.  Recognition of GU‐rich polyadenylation regulatory elements by human CstF‐64 protein , 2003, The EMBO journal.

[10]  D. Hovorun,et al.  Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures. , 2003, Nucleic acids research.

[11]  D. Gautheret,et al.  Sequence determinants in human polyadenylation site selection , 2003, BMC Genomics.

[12]  Jeffrey Wilusz,et al.  Upstream Elements Present in the 3′-Untranslated Region of Collagen Genes Influence the Processing Efficiency of Overlapping Polyadenylation Signals* , 2002, The Journal of Biological Chemistry.

[13]  Jeffrey Wilusz,et al.  Downstream sequence elements with different affinities for the hnRNP H/H' protein influence the processing efficiency of mammalian polyadenylation signals. , 2002, Nucleic acids research.

[14]  M. Edmonds,et al.  A history of poly A sequences: from formation to factors to function. , 2002, Progress in nucleic acid research and molecular biology.

[15]  Tala Bakheet,et al.  ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins , 2001, Nucleic Acids Res..

[16]  N. Proudfoot,et al.  Transcriptional termination and coupled polyadenylation in vitro , 2000, The EMBO journal.

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

[18]  C R Cantor,et al.  In silico detection of control signals: mRNA 3'-end-processing sequences in diverse species. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  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.

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

[21]  J. Manley,et al.  Mechanism and regulation of mRNA polyadenylation. , 1997, Genes & development.

[22]  M. Hentze,et al.  Starting at the Beginning, Middle, and End: Translation Initiation in Eukaryotes , 1997, Cell.

[23]  M. Wickens,et al.  Life and death in the cytoplasm: messages from the 3' end. , 1997, Current opinion in genetics & development.

[24]  Sophie Schbath,et al.  An Efficient Statistic to Detect Over-and Under-Represented Words in DNA Sequences , 1997, J. Comput. Biol..

[25]  B. Graveley,et al.  RNA structure is a critical determinant of poly(A) site recognition by cleavage and polyadenylation specificity factor , 1996, Molecular and cellular biology.

[26]  S. Peltz,et al.  Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. , 1996, Annual review of biochemistry.

[27]  C. Y. Chen,et al.  AU-rich elements: characterization and importance in mRNA degradation. , 1995, Trends in biochemical sciences.

[28]  M. Wollerton,et al.  Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved. , 1995, The EMBO journal.

[29]  J. Wilusz,et al.  Cleavage site determinants in the mammalian polyadenylation signal. , 1995, Nucleic acids research.

[30]  J. Wilusz,et al.  The G-rich auxiliary downstream element has distinct sequence and position requirements and mediates efficient 3' end pre-mRNA processing through a trans-acting factor. , 1995, Nucleic acids research.

[31]  T. Shenk,et al.  The 64-kilodalton subunit of the CstF polyadenylation factor binds to pre-mRNAs downstream of the cleavage site and influences cleavage site location , 1994, Molecular and cellular biology.

[32]  Fan Chen,et al.  Sequence and position requirements for uridylate-rich downstream elements of polyadenylation signals , 1994, Nucleic Acids Res..

[33]  G. Edwalds-Gilbert,et al.  3' RNA processing efficiency plays a primary role in generating termination-competent RNA polymerase II elongation complexes , 1993, Molecular and cellular biology.

[34]  J. Alwine,et al.  Elements upstream of the AAUAAA within the human immunodeficiency virus polyadenylation signal are required for efficient polyadenylation in vitro , 1992, Molecular and cellular biology.

[35]  B. Cullen,et al.  Efficient polyadenylation within the human immunodeficiency virus type 1 long terminal repeat requires flanking U3-specific sequences , 1991, Journal of virology.

[36]  J. Alwine,et al.  The human immunodeficiency virus type 1 polyadenylylation signal: a 3' long terminal repeat element upstream of the AAUAAA necessary for efficient polyadenylylation. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[37]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[38]  J. Alwine,et al.  Efficiency of utilization of the simian virus 40 late polyadenylation site: effects of upstream sequences , 1989, Molecular and cellular biology.

[39]  N. Proudfoot,et al.  Definition of an efficient synthetic poly(A) site. , 1989, Genes & development.

[40]  T. Shenk,et al.  A 64 kd nuclear protein binds to RNA segments that include the AAUAAA polyadenylation motif , 1988, Cell.

[41]  J. Manley,et al.  Requirements for accurate and efficient mRNA 3' end cleavage and polyadenylation of a simian virus 40 early pre-RNA in vitro , 1987, Molecular and cellular biology.

[42]  R. Amann,et al.  Predictive Identification of Exonic Splicing Enhancers in Human Genes , 2022 .