Promoter usage and alternative splicing.

Recent findings justify a renewed interest in alternative splicing (AS): the process is more a rule than an exception as it affects the expression of 60% of human genes; it explains how a vast mammalian proteomic complexity is achieved with a limited number of genes; and mutations in AS regulatory sequences are a widespread source of human disease. AS regulation not only depends on the interaction of splicing factors with their target sequences in the pre-mRNA but is coupled to transcription. A clearer picture is emerging of the mechanisms by which transcription affects AS through promoter identity and occupation. These mechanisms involve the recruitment of factors with dual functions in transcription and splicing (i.e. that contain both functional domains and hence link the two processes) and the control of RNA polymerase II elongation.

[1]  A. Kornblihtt,et al.  Influence of Polymerase II Processivity on Alternative Splicing Depends on Splice Site Strength* , 2003, Journal of Biological Chemistry.

[2]  A. Kornblihtt,et al.  Transcriptional Activators Differ in Their Abilities to Control Alternative Splicing* , 2002, The Journal of Biological Chemistry.

[3]  A. Kornblihtt,et al.  Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. O’Malley,et al.  CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing , 2004, Molecular and Cellular Biology.

[5]  T. Maniatis,et al.  An extensive network of coupling among gene expression machines , 2002, Nature.

[6]  D. Bentley,et al.  RNA Polymerase II Carboxy-Terminal Domain Phosphorylation Is Required for Cotranscriptional Pre-mRNA Splicing and 3′-End Formation , 2004, Molecular and Cellular Biology.

[7]  M. Garcia-Blanco,et al.  MAZ Elements Alter Transcription Elongation and Silencing of the Fibroblast Growth Factor Receptor 2 Exon IIIb* , 2004, Journal of Biological Chemistry.

[8]  M. Garcia-Blanco,et al.  The Transcription Elongation Factor CA150 Interacts with RNA Polymerase II and the Pre-mRNA Splicing Factor SF1 , 2001, Molecular and Cellular Biology.

[9]  A. Lamond,et al.  WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes. , 1998, Genes & development.

[10]  D. Bentley The mRNA assembly line: transcription and processing machines in the same factory. , 2002, Current opinion in cell biology.

[11]  R. Tjian,et al.  Transcription of herpes simplex virus tk sequences under the control of wild-type and mutant human RNA polymerase I promoters , 1985, Molecular and cellular biology.

[12]  Bert W O'Malley,et al.  Coordinate Regulation of Transcription and Splicing by Steroid Receptor Coregulators , 2002, Science.

[13]  Mark Groudine,et al.  Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells , 2004, Nature Structural &Molecular Biology.

[14]  A. Kornblihtt,et al.  Alternative splicing: multiple control mechanisms and involvement in human disease. , 2002, Trends in genetics : TIG.

[15]  A. Yuryev,et al.  The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Manley,et al.  The C-Terminal Domain of RNA Polymerase II Functions as a Phosphorylation-Dependent Splicing Activator in a Heterologous Protein , 2005, Molecular and Cellular Biology.

[17]  P Cramer,et al.  Functional association between promoter structure and transcript alternative splicing. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

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

[19]  M. Beato,et al.  Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4* , 2004, Journal of Biological Chemistry.

[20]  P. Puigserver,et al.  Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. , 2000, Molecular cell.

[21]  B. Blencowe,et al.  Transcriptional Activators Control Splicing and 3′-End Cleavage Levels* , 2003, Journal of Biological Chemistry.

[22]  K. O'hare,et al.  Role of RNA polymerase II carboxy-terminal domain in coordinating transcription with RNA processing. , 1998, Cold Spring Harbor symposia on quantitative biology.

[23]  A. Kornblihtt,et al.  Antagonistic effects of T‐Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing , 2001, The EMBO journal.

[24]  D. Cleveland,et al.  Specificity of RNA maturation pathways: RNAs transcribed by RNA polymerase III are not substrates for splicing or polyadenylation , 1987, Molecular and cellular biology.

[25]  M. Wickens,et al.  The C-terminal domain of RNA polymerase II couples mRNA processing to transcription , 1997, Nature.

[26]  M. Lai,et al.  A Human Papillomavirus E2 Transcriptional Activator , 1999, The Journal of Biological Chemistry.

[27]  A. Travers,et al.  Chromatin modification by DNA tracking. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Kornblihtt,et al.  A slow RNA polymerase II affects alternative splicing in vivo. , 2003, Molecular cell.

[29]  Kai Lin,et al.  The WW Domain-Containing Proteins Interact with the Early Spliceosome and Participate in Pre-mRNA Splicing In Vivo , 2004, Molecular and Cellular Biology.

[30]  Antonin Morillon,et al.  Gene loops juxtapose promoters and terminators in yeast , 2004, Nature Genetics.

[31]  T. Oas,et al.  Phosphorylation of RNA polymerase II CTD fragments results in tight binding to the WW domain from the yeast prolyl isomerase Ess1. , 2001, Biochemistry.

[32]  B. O’Malley,et al.  Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. Greenleaf,et al.  The Splicing Factor, Prp40, Binds the Phosphorylated Carboxyl-terminal Domain of RNA Polymerase II* , 2000, The Journal of Biological Chemistry.

[34]  M. Ares,et al.  Perturbation of transcription elongation influences the fidelity of internal exon inclusion in Saccharomyces cerevisiae. , 2003, RNA.

[35]  Xiao Zhen Zhou,et al.  Pin1 modulates the structure and function of human RNA polymerase II. , 2003, Genes & development.

[36]  F. Tronche,et al.  Combinatorial Complexity of 5′ Alternative Acetylcholinesterase Transcripts and Protein Products*[boxs] , 2004, Journal of Biological Chemistry.

[37]  K. Neugebauer,et al.  On the importance of being co-transcriptional , 2002, Journal of Cell Science.

[38]  G. C. Roberts,et al.  Co-transcriptional commitment to alternative splice site selection. , 1998, Nucleic acids research.

[39]  A. Hartmann,et al.  SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. , 1998, Nucleic acids research.

[40]  M. Rosbash,et al.  T7 RNA polymerase-directed transcripts are processed in yeast and link 3' end formation to mRNA nuclear export. , 2002, RNA.

[41]  A. Kornblihtt,et al.  Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. , 1999, Molecular cell.

[42]  I. Graham,et al.  Effects of RNA secondary structure on alternative splicing of Pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase? , 1988, Cell.

[43]  D. Black Mechanisms of alternative pre-messenger RNA splicing. , 2003, Annual review of biochemistry.

[44]  B. Frey,et al.  Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. , 2004, Molecular cell.

[45]  A. Kornblihtt,et al.  Promoter Architecture Modulates CFTR Exon 9 Skipping* , 2003, The Journal of Biological Chemistry.

[46]  S. Berget,et al.  Participation of the C-Terminal Domain of RNA Polymerase II in Exon Definition during Pre-mRNA Splicing , 2000, Molecular and Cellular Biology.

[47]  N. Proudfoot Dawdling polymerases allow introns time to splice , 2003, Nature Structural Biology.