Mount Lab Reading Room

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General reviews (on splicing, splicing regulation or splicing mechanisms, whatever we're interested in)

Wang and Burge 2008 "Splicing regulation: From a parts list of regulatory elements to an integrated splicing code." A review of splicing regulatory elements (the "splicing code"). (PDF, RNA, PubMed)

Reddy 2007 "Alternative Splicing of Pre-Messenger RNAs in Plants in the Genomic Era" A review of alternative splicing in plants. (PDF PubMed)

Kazan 2004 "Alternative splicing and proteome diversity in plants: the tip of the iceberg has just emerged" A review of alternative splicing in plants. (PDF PubMed)

Garcia-Blanco 2004 "Alternative splicing in disease and therapy," A review of alternative splicing with an emphasis on clinical applications. (PDF)

Ladd & Cooper 2002 "Finding signals that regulate alternative splicing in the postgenomic era" A review of alternative splicing with an emphasis of known cis-acting elements.(PDF)(Genome Biology)(PubMed)

Zhi-Ming Zheng's review of mammalian alternative splicing focuses on ESEs.

Brow 2002 "Allosteric Cascade of Spliceosome Activation," A review of splicing mechanisms.

Alternative Splicing data - microarrays

Castle et al. 2003 "Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing" The approach. (PDF, Genome Biology, PubMed)

Pan et al. 2004 "Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform." The original alternative splicing microarray paper from the Blencowe group. (PDF, PubMed)

Pan et al. 2005 "Alternative splicing of conserved exons is frequently species-specific in human and mouse." The Blencowe group. (PDF, PubMed)

Castle et al. 2008 "Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines" The most recent results from the Rosetta group. (PDF, Nature Genetics, PubMed)

Comparative proteomics, genomics and genefinding

Jurica & Moore 2003 "Awash in a sea of proteins," A review of spliceosome proteomic data.

Computational Prediction of Protein-coding Genes. Michael Zhang's excellent 2002 review of the status of Genefinding.

Lorkovic et al. (Barta lab) . This provides a survey of Arabidopsis RNA-binding proteins: RRM and KH domain proteins.

Modrek & Lee 2003 "Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss." Comparative data indicates that exons that are only included in alternatively spliced forms (as opposed to the constitutive or major transcript form) are mostly not conserved and thus are the product of recent exon creation or loss events.

Goren et al. 2006. "Comparative Analysis Identifies Exonic Splicing Regulatory Sequences -- The Complex Definition of Enhancers and Silencers" (PubMed   Molecular Cell PDF) introduces the term ESR for exonic regulatory sequences and studies some of their properties. There are no surprises here, but the paper provides a key confirmation of the importance of position within the exon to ESR function.

Intron evolution

Following the original article by Modrek and Lee, Yi Xing and Chris Lee have written extensively on the evolution of splicing, particularly the origins of new exons. A recent article that cites their earlier work is Xing and Lee 2006. "Alternative splicing and RNA selection pressure -- evolutionary consequences for eukaryotic genomes" (PubMed Nature Reviews Genetics PDF).

SR proteins (esp. in plants)

Balasubramanian et al. (Weigel lab). 2006. "Potent Induction of Arabidopsis thaliana Flowering by Elevated Growth Temperature." reveals that SR proteins and other splicing regulators (including RSZP22a, La (At5g46250), SCL33, SRp30 and Y14) are especially responsive. (PubMed, PLOS Genetics, PDF, data)

Huang and Steitz 2005. "SRprises along a messenger's journey," a brief and timely review of SR proteins focusing on roles other than splicing. (PDF, NCBI).

Kalyna and Barta. 2004. A plethora of plant serine/arginine-rich proteins: redundancy or evolution of novel gene functions? (PDF, NCBI)

Reddy. 2004. Plant serine/arginine-rich proteins and their role in pre-mRNA splicing.(PDF, NCBI)

Balasubramanian 2005 (Ph.D. thesis on SR45)

Ram and Ast. "SR proteins: a foot on the exon before the transition from intron to exon definition" (PubMed, PDF)

Exonic Splicing Regulators (ESRs, including ESEs and ESSs)

Goren et al. 2006. (PubMed   Molecular Cell PDF) introduces " ESR" for exonic regulatory sequences

Wang, Xiao, Van Nostrand and Burge. 2006. "General and Specific Functions of Exonic Splicing Silencers in Splicing Control." Molec. Cell 23: 61-70. (PubMed Molecular Cell PDF Suppl. data).

Blencowe 2000. A review of exonic splicing enhancers (ESEs), including their mechanism of action, diversity, role in human genetic disease and recognition by SR proteins.

Cartegni (with Michael Zhang) This paper describes ESEfinder, a tool for identifying ASF/SF2, SC35, SRp40 and SRp55 sites using matrices based primarily on the data of Liu et al (see below).

Cartegni (Krainer lab) The difference in an ESE accounts for the functional difference between the human SMN1 and SMN2 genes.

Graveley 2000 (review) "Sorting out the complexity of SR protein functions." RNA 6:1197-1211

Liu et al. 1998 (Krainer lab) This paper describes the identification of (human) ESEs by an in vitro selection assay.

Cartegni et al. This is a comprehensive review about the possible effect of synonymous substitutions on splicing.

Fairbrother et al."Predictive identification of exonic splicing enhancers in human genes." Science 2002. This paper describes the use of a statistical approach to identify candidate human ESE motifs and the verification of their activity.

Stadler et al."Inference of splicing regulatory activities by sequence neighborhood analysis." PLOS Genetics 2006. This paper describes a method for generalizing ESE and ESS predictions to similar sequences.
PMID: 17121466 PDF PLOS genetics

Genetic background and complexity

Nissim-Rafinia & Kerem 2002 Splicing regulation as a potential genetic modifier. (PubMed PDF)

Nissim-Rafinia & Kerem 2005 The splicing machinery is a genetic modifier of disease severity. (PubMed PDF)

Glazier et al. 2003. Finding Genes that Underlie Complex Traits. Science 298:2345. This paper talks about how common complex traits are and critieria for the identification of genes involved in complex traits.

Nadeau 2003. Modifying the Message. Science :927-301928. This is a commentary on:

Buchner et al. 2003. SCNM1,a Putative RNA Splicing Factor That Modifies Disease Severity in Mice. Science 301:967-969. A difference between strains of mice in the expression of a splice donor site of the sodium channel gene Scn8a turns out to be in an RNA-binding protein.

Suppressible splicing mutations in Arabidopsis.

Sablowski and Meyerowitz Temperature-Sensitive Splicing in the Floral Homeotic Mutant apetala3-1

Yi and Jack Description of the ap3-11 allele, a partial revertant of the 5' splice site mutation ap3-1 due to improvement a the branch site upstream of the same exon.

Genome-wide analysis of alternative splicing in Arabidopsis or other plants.

Wang and Brendel. 2006. Genomewide comparative analysis of alternative splicing in plants (PubMed, PNAS, PDF). A global analysis of alternative splicing, introduces the Alternative Splicing in Plants (ASIP) database.

Haas et al. 2005. Complete annotation of the Arabidopsis genome: methods, tools, protocols and the final release. BMC Biol.3::7. (PubMed)

Iida et al. 2004. Genome-wide analysis of alternative pre-mRNA splicing in Arabidopsis thaliana based on full-length cDNA sequences. Nucleic Acids Res. 32:5096 (PubMed)

Nonsense-mediated decay (NMD) and alternative splicing.

Connections between NMD and regulated unproductive splicing (RUS) were emphasized Green and Brenner (PubMed) in a series of articles in 2003-2004.

With respect to Arabidopsis, In 2005, Hori and Watanabe published in Plant Journal that an Arabidopsis upf3 mutation is viable but leads to the accumulation of aberrantly spliced RNAs (MedLine Plant J. PDF). Then, Yoine et al. have showed that UPF1 is essential for growth (PubMed Plant Cell Physiol. PDF) and that low-beta-amylase1 , (lba1), a missense mutation in UPF1, causes pleiotropic effects related to sugar metabolism (PubMed Plant J. PDF). A recent paper (Schoning et al. 2008; PubMed, NAR, PDF) describes the use of viable upf1 alleles in an analysis of glycine-rich RNA-binding protein cross-regulation.

There are now lots of tools to study nonsense-mediated decay in Arabidopsis.

The situation in Drosophila is reviewed nicely by Conti and Izzauralde (PubMed).

Pan et al. (2006) use alternative splicing microarray analysis in the mouse to argue against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression (PDF, Genes & Dev. , PubMed).

Blencowe 2006. Alternative splicing: new insights from global analyses.(PubMed Cell PDF)

Darnell has studied the regulation of alternative splicing by the protein NOVA in a series of papers (Ule et al. 2005 and 2006 [ Nature])

Alternative RNA processing or splice site selection in Arabidopsis (mostly FCA)

Macknight-FCA.pdf This is the orginal description of FCA as an alternatively spliced RNA-binding protein.

Lewandowska-U12.pdf An analysis of splicing signals in a few Arabidopsis U12 intronss.

Macknight-FCA02.pdf This is the 2002 paper showing the regulation of FCA alternative splicing.

Quesada et al. 2003 This paper demonstrates FCA autoregulation.

Simpson et al. 2003 This 2003 paper shows that FY, which is homologous to 3' end formation factors Pfs2p and CstF50, functions in 3' end formation in FCA autoregulation.


Cheng et al. (Chen lab): Arabidopsis HEN4 and HUA1 affect AG pre-mRNA processing.

Blazquez et al. (Weigel lab) "A thermosensory pathway controlling flowering time in Arabidopsis thaliana" This paper shows that the flowering time of fca1 mutants is unaffected by temperature, implying that the RNA-binding protein FCA mediates thermosensory pathway controlling flowering time.

Razem et al. 2006. "The RNA-binding protein FCA is an abscisic acid receptor." Nature 439, 290-294.
FCA protein binds ABA, and ABA affects both FCA autoregulation in vivo and its interaction with FY in vitro. (PubMed ID16421562, Nature, PDF)

Last modified March 15, 2009.