The SR protein family
© BioMed Central Ltd 2009
Published: 27 October 2009
The processing of pre-mRNAs is a fundamental step required for the expression of most metazoan genes. Members of the family of serine/arginine (SR)-rich proteins are critical components of the machineries carrying out these essential processing events, highlighting their importance in maintaining efficient gene expression. SR proteins are characterized by their ability to interact simultaneously with RNA and other protein components via an RNA recognition motif (RRM) and through a domain rich in arginine and serine residues, the RS domain. Their functional roles in gene expression are surprisingly diverse, ranging from their classical involvement in constitutive and alternative pre-mRNA splicing to various post-splicing activities, including mRNA nuclear export, nonsense-mediated decay, and mRNA translation. These activities point up the importance of SR proteins during the regulation of mRNA metabolism.
Gene organization and evolutionary history
Human genes encoding SR proteins
More recent genome-wide studies have identified several other RS-domain-containing proteins, most of wh ich are conserved in higher eukaryotes and function in pre-mRNA splicing or RNA metabolism . Because of differences in domain structure, lack of mAb104 recognition, or lack of a prototypical RRM, these proteins are referred to as SR-like or SR-related proteins. An extensive list of SR-related proteins and their functional roles in RNA metabolism was recently discussed .
Characteristic structural features
All SR proteins share two main structural features: the RS domain and at least one RRM (Figure 1). For the majority of SR proteins with two RNA-binding domains, the second is a poor match to the RRM consensus and is referred to as an RRM homolog (RRMH). The only exception is 9G8, which contains an RRM and a zinc-knuckle domain that is thought to contact the RNA . In the cases where it has been determined, SR proteins have specific, yet degenerate RNA-binding specificities [18, 19]. The RS domains of SR proteins participate in protein interactions with a number of other RS-domain-containing splicing factors [20, 21]. These include other SR proteins, SR-related proteins , and components of the general splicing machinery [20, 21, 23–25]. Furthermore, the RS domain can function as a nuclear localization signal by mediating the interaction with the SR protein nuclear import receptor, transportin-SR [26–28].
Localization and function
In classic cases of alternative splicing, it has been shown that cis-acting RNA sequence elements, known as splicing enhancers, increase exon inclusion by serving as sites for recruitment of the splicing machinery - the spliceosome - which is a complex of ribonucleoprotein splicing factors, such as U1 and U2 small nuclear ribonucleoproteins (snRNPs), and their associated proteins, such as U2 auxiliary factor (U2AF), that splices exons together and releases the intron RNA. Splicing enhancers are usually located within the regulated exon, and are thus known as exonic splicing enhancers (ESEs) [41, 42]. ESEs are usually recognized by at least one member of the SR protein family and recruit the splicing machinery to the adjacent intron [9, 41, 42]. SR proteins act at several steps during the splicing reaction [4, 5, 8, 43–45] and require phosphorylation for efficient splice-site recognition and dephosphorylation for splicing catalysis [46, 47]. A number of SR protein kinases have been identified that specifically phosphorylate serine residues within the RS domain of SR proteins. These include SR protein kinase 1 (SRPK1) , Clk/Sty kinase , cdc2p34 , and topoisomerase . Surprisingly, binding sites for SR proteins are not only limited to alternatively spliced exons, but have also been verified for exons of constitutively spliced pre-mRNAs [52, 53]. It is therefore likely that SR proteins bind to sequences found in most, if not all, exons.
In addition to their exon-dependent functions, SR proteins have activities that do not require interaction with exon sequences . The role of the exon-independent function may be to promote the pairing of 5' and 3' splice sites across the intron or to facilitate the incorporation of the tri-snRNP U4/U6•U5 into the spliceosome  (Figure 5b). U4/U6•U5 is a complex of snRNPs that contains the splicing activity. Although the RRM of the SR protein is essential for its exon-independent activity , it is likely that SR proteins interact with the partially assembled spliceosome or the tri-snRNP through RS domain contacts.
One striking feature of SR proteins is their prevalent location within the pre-mRNA. In nearly all cases SR proteins have been found to interact with exonic sequences of the pre-mRNA. This is a surprising finding considering the fact that their relatively promiscuous binding specificity predicts that introns are littered with potential SR-protein-binding sites. The fact that SR proteins are mainly observed to bind within exonic sequences suggests that additional requirements need to be met for functional SR protein binding to the pre-mRNA. There are, however, some instances of SR proteins binding within the intron, where they function as negative regulators of splicing. The best-characterized example occurs during adenovirus infection . In this case, splicing is repressed by the binding of the SR protein SF2/ASF to an intronic repressor element located upstream of the 3' splice site branchpoint sequence in the adenovirus pre-mRNA. When bound to the repressor element, SF2/ASF prevents the recruitment of the snRNP U2 to the branchpoint sequence, thereby inactivating the 3' splice site (Figure 5c). Other studies have provided further support for the idea that SR proteins bound to introns generally interfere with the productive assembly of spliceosomes . These observations show that exonic splicing enhancers not only function in exon and splice-site recognition, but also act as barriers to prevent exon skipping.
Role of SR proteins in mRNA export
SR protein involvement in translation
SR proteins have been shown to influence translation either indirectly or directly. For example, the splicing activity of SF2/ASF influences alternative splicing of the pre-mRNA for the protein kinase MNK2, a kinase that regulates translation initiation. High levels of SF2/ASF promote the production of an MNK2 mRNA isoform that enhances cap-dependent translation, whereas low levels achieve the opposite . SF2/ASF is also involved in regulating translation directly. It has been shown to associate with polyribosome fractions isolated from cytoplasmic extracts and to enhance the translation efficiency of an ESE-containing luciferase reporter , apparently through mediating the recruitment of components of mTOR (mammalian target of rapamycin) signaling pathway (Figure 6b). As a result of this recruitment, a competitive inhibitor of cap-dependent translation is released .
Importantly, other SR proteins have also been reported to function in translation. SRp20 promotes translation of a viral RNA initiated at an internal ribosome entry site , and 9G8 increases translation efficiency of unspliced mRNA containing a constitutive transport element .
The functional characterization of SR proteins has revealed a wealth of information, placing SR proteins in the context of regulating constitutive and alternative pre-mRNA splicing, mediating efficient transport of mRNAs, and modu lat ing mRNA translation. As such, SR proteins could easily be mistaken for 'Jacks of all trades, masters of none' in mRNA metabolism. However, many studies have demon strated their essential presence in the cell, even with occasional redundancies. Given the enormous functional real estate this family of proteins covers, one is now pressed to find out how it is possible to transition these proteins between their involvements in the various steps of mRNA processing. Clearly, reversible modification, such as serine phosphorylation within the RS domain, is likely to be the ticket for SR protein functional flexibility . The challenge will be to determine the extent and dynamics of such modifications within SR proteins specifically involved in one of these activities and whether changes in modification lend support to the existence of an SR protein-modification code, perhaps similar in principle to the now well-described histone-modification code .
An old foe makes up another challenge: SR protein structure. For more than 15 years attempts have been made to obtain high-resolution structures of SR proteins. So far, these attempts have failed because of problems of low solubility and the likely heterogeneity of RS-domain modifications. As a first step towards gaining ground in this endeavor, clever modification approaches have been used to obtain a high-resolution structure of the SR protein RRM domain. This is a significant first step. However, the much more elusive RS domain is still the big prize, requiring further creative approaches and manipulations to freeze this seemingly unstructured domain in a conformation that permits its structural elucidation.
A different and experimentally challenging puzzle to address is the balance between the relatively low RNA-binding specificity exhibited by SR proteins and their usually specific functional impact. Given that SR proteins generally associate with exon sequences, it is likely that their interaction with the RNA is often aided by other factors. This suggestion is supported by the observation that at least 75% of the nucleotides in a typical human exon are part of sequence motifs that have been found to influence splicing, presumably through the binding of splicing activators, such as SR proteins, or the binding of splicing repressors, such as heterogeneous nuclear RNPs . For example, it is possible that the binding of SR proteins to pre-mRNA is only guaranteed if they are flanked by spliceosomal components such as U2 snRNP auxiliary factor or U1 snRNP, thus establishing a network of protein-protein and protein-RNA interactions. The establishment of such a network would then permit the stable association of SR proteins with many different target sequences, thus enabling SR proteins to recognize the thousands of different exons present in higher eukaryotes . Therefore, the relatively low RNA-binding specificity may have evolved to uphold the suitability of SR proteins to participate effectively in multiple RNA-processing events.
Clearly, SR proteins make up a family of regulators with important functions in RNA metabolism. This realization is exemplified when considering that changes in SR protein function or abundance have frequently been associated with human disease. For example, SF2/ASF has been described as a proto-oncogene  and the misregulation of alternative splicing has been associated with several types of cancer . While the involvement of SR proteins in various aspects of gene expression has been shown to be widespread, it would not be surprising if they emerge as critical players in other important biological processes.
We are grateful to the Hertel laboratory for helpful comments on the manuscript and Lin Li and Rozanne Sandri-Goldin for providing images of SR protein speckles. Our research is supported by NIH grant GM 62287 (KJH).
- Chou TB, Zachar Z, Bingham PM: Developmental expression of a regulatory gene is programmed at the level of splicing. EMBO J. 1987, 6: 4095-4104.PubMedPubMed Central
- Boggs RT, Gregor P, Idriss S, Belote JM, McKeown M: Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene. Cell. 1987, 50: 739-747. 10.1016/0092-8674(87)90332-1.PubMedView Article
- Amrein H, Gorman M, Nothiger R: The sex-determining gene tra-2 of Drosophila encodes a putative RNA binding protein. Cell. 1988, 55: 1025-1035. 10.1016/0092-8674(88)90247-4.PubMedView Article
- Ge H, Manley JL: A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro. Cell. 1990, 62: 25-34. 10.1016/0092-8674(90)90236-8.PubMedView Article
- Krainer AR, Conway GC, Kozak D: Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev. 1990, 4: 1158-1171. 10.1101/gad.4.7.1158.PubMedView Article
- Fu XD, Maniatis T: The 35-kDa mammalian splicing factor SC35 mediates specific interactions between U1 and U2 small nuclear ribonucleoprotein particles at the 3' splice site. Proc Natl Acad Sci USA. 1992, 89: 1725-1729. 10.1073/pnas.89.5.1725.PubMedPubMed CentralView Article
- Roth MB, Zahler AM, Stolk JA: A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription. J Cell Biol. 1991, 115: 587-596. 10.1083/jcb.115.3.587.PubMedView Article
- Zahler AM, Lane WS, Stolk JA, Roth MB: SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 1992, 6: 837-847. 10.1101/gad.6.5.837.PubMedView Article
- Graveley BR: Sorting out the complexity of SR protein functions. RNA. 2000, 6: 1197-1211. 10.1017/S1355838200000960.PubMedPubMed CentralView Article
- Boucher L, Ouzounis CA, Enright AJ, Blencowe BJ: A genome-wide survey of RS domain proteins. RNA. 2001, 7: 1693-1701.PubMedPubMed Central
- Long JC, Caceres JF: The SR protein family of splicing factors: master regulators of gene expression. Biochem J. 2009, 417: 15-27. 10.1042/BJ20081501.PubMedView Article
- Lutzelberger M, Gross T, Kaufer NF: Srp2, an SR protein family member of fission yeast: in vivo characterization of its modular domains. Nucleic Acids Res. 1999, 27: 2618-2626. 10.1093/nar/27.13.2618.PubMedPubMed CentralView Article
- Gross T, Richert K, Mierke C, Lutzelberger M, Kaufer NF: Identification and characterization of srp1, a gene of fission yeast encoding a RNA binding domain and a RS domain typical of SR splicing factors. Nucleic Acids Res. 1998, 26: 505-511. 10.1093/nar/26.2.505.PubMedPubMed CentralView Article
- Kress TL, Krogan NJ, Guthrie C: A single SR-like protein, Npl3, promotes pre-mRNA splicing in budding yeast. Mol Cell. 2008, 32: 727-734. 10.1016/j.molcel.2008.11.013.PubMedPubMed CentralView Article
- Plass M, Agirre E, Reyes D, Camara F, Eyras E: Co-evolution of the branch site and SR proteins in eukaryotes. Trends Genet. 2008, 24: 590-594. 10.1016/j.tig.2008.10.004.PubMedView Article
- Escobar AJ, Arenas AF, Gomez-Marin JE: Molecular evolution of serine/arginine splicing factors family (SR) by positive selection. In Silico Biol. 2006, 6: 347-350.PubMed
- Cavaloc Y, Popielarz M, Fuchs JP, Gattoni R, Stevenin J: Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family. EMBO J. 1994, 13: 2639-2649.PubMedPubMed Central
- Liu HX, Zhang M, Krainer AR: Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev. 1998, 12: 1998-2012. 10.1101/gad.12.13.1998.PubMedPubMed CentralView Article
- Liu HX, Chew SL, Cartegni L, Zhang MQ, Krainer AR: Exonic splicing enhancer motif recognized by human SC35 under splicing conditions. Mol Cell Biol. 2000, 20: 1063-1071. 10.1128/MCB.20.3.1063-1071.2000.PubMedPubMed CentralView Article
- Wu JY, Maniatis T: Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell. 1993, 75: 1061-1070. 10.1016/0092-8674(93)90316-I.PubMedView Article
- Kohtz JD, Jamison SF, Will CL, Zuo P, Lührmann R, Garcia-Blanco MA, Manley JL: Protein-protein interactions and 5' splice site recognition in mammalian mRNA precursors. Nature. 1994, 368: 119-124. 10.1038/368119a0.PubMedView Article
- Blencowe BJ, Bowman JA, McCracken S, Rosonina E: SR-related proteins and the processing of messenger RNA precursors. Biochem Cell Biol. 1999, 77: 277-291. 10.1139/bcb-77-4-277.PubMedView Article
- Teigelkamp S, Mundt C, Achsel T, Will CL, Luhrmann R: The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p. RNA. 1997, 3: 1313-1326.PubMedPubMed Central
- Fetzer S, Lauber J, Will CL, Luhrmann R: The [U4/U6.U5] tri-snRNP-specific 27K protein is a novel SR protein that can be phosphorylated by the snRNP-associated protein kinase. RNA. 1997, 3: 344-355.PubMedPubMed Central
- Makarova OV, Makarov EM, Luhrmann R: The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. EMBO J. 2001, 20: 2553-2563. 10.1093/emboj/20.10.2553.PubMedPubMed CentralView Article
- Cáceres JF, Misteli T, Screaton GR, Spector DL, Krainer AR: Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J Cell Biol. 1997, 138: 225-238. 10.1083/jcb.138.2.225.PubMedPubMed CentralView Article
- Kataoka N, Bachorik JL, Dreyfuss G: Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol. 1999, 145: 1145-1152. 10.1083/jcb.145.6.1145.PubMedPubMed CentralView Article
- Lai MC, Lin RI, Huang SY, Tsai CW, Tarn WY: A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem. 2000, 275: 7950-7957. 10.1074/jbc.275.11.7950.PubMedView Article
- Zhou P, Lugovskoy AA, Wagner G: A solubility-enhancement tag (SET) for NMR studies of poorly behaving proteins. J Biomol NMR. 2001, 20: 11-14. 10.1023/A:1011258906244.PubMedView Article
- Hargous Y, Hautbergue GM, Tintaru AM, Skrisovska L, Golovanov AP, Stevenin J, Lian LY, Wilson SA, Allain FH: Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8. EMBO J. 2006, 25: 5126-5137. 10.1038/sj.emboj.7601385.PubMedPubMed CentralView Article
- Cavaloc Y, Bourgeois CF, Kister L, Stevenin J: The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers. RNA. 1999, 5: 468-483. 10.1017/S1355838299981967.PubMedPubMed CentralView Article
- Schaal TD, Maniatis T: Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. Mol Cell Biol. 1999, 19: 1705-1719.PubMedPubMed CentralView Article
- Spector DL: Macromolecular domains within the cell nucleus. Annu Rev Cell Biol. 1993, 9: 265-315. 10.1146/annurev.cb.09.110193.001405.PubMedView Article
- Spector DL: Nuclear organization and gene expression. Exp Cell Res. 1996, 229: 189-197. 10.1006/excr.1996.0358.PubMedView Article
- Manley JL, Tacke R: SR proteins and splicing control. Genes Dev. 1996, 10: 1569-1579. 10.1101/gad.10.13.1569.PubMedView Article
- Fu X-D: The superfamily of arginine/serine-rich splicing factors. RNA. 1995, 1: 663-680.PubMedPubMed Central
- Hedley ML, Amrein H, Maniatis T: An amino acid sequence motif sufficient for subnuclear localization of an arginine/serine-rich splicing factor. Proc Natl Acad Sci USA. 1995, 92: 11524-11528. 10.1073/pnas.92.25.11524.PubMedPubMed CentralView Article
- Jimenez-Garcia LF, Spector DL: In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism. Cell. 1993, 73: 47-59. 10.1016/0092-8674(93)90159-N.PubMedView Article
- Misteli T, Caceres JF, Spector DL: The dynamics of a pre-mRNA splicing factor in living cells. Nature. 1997, 387: 523-527. 10.1038/387523a0.PubMedView Article
- Misteli T, Caceres JF, Clement JQ, Krainer AR, Wilkinson MF, Spector DL: Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J Cell Biol. 1998, 143: 297-307. 10.1083/jcb.143.2.297.PubMedPubMed CentralView Article
- Blencowe BJ: Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem Sci. 2000, 25: 106-110. 10.1016/S0968-0004(00)01549-8.PubMedView Article
- Black DL: Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003, 72: 291-336. 10.1146/annurev.biochem.72.121801.161720.PubMedView Article
- Fu X-D: Specific commitment of different pre-mRNAs to splicing by single SR proteins. Nature. 1993, 365: 82-85. 10.1038/365082a0.PubMedView Article
- Roscigno RF, Garcia-Blanco MA: SR proteins escort the U4/U6.U5 tri-snRNP to the spliceosome. RNA. 1995, 1: 692-706.PubMedPubMed Central
- Chew SL, Liu HX, Mayeda A, Krainer AR: Evidence for the function of an exonic splicing enhancer after the first catalytic step of pre-mRNA splicing. Proc Natl Acad Sci USA. 1999, 96: 10655-10660. 10.1073/pnas.96.19.10655.PubMedPubMed CentralView Article
- Mermoud JE, Cohen P, Lamond AI: Ser/Thr-specific protein phosphatases are required for both catalytic steps of pre-mRNA splicing. Nucleic Acids Res. 1992, 20: 5263-5269. 10.1093/nar/20.20.5263.PubMedPubMed CentralView Article
- Mermoud JE, Cohen PT, Lamond AI: Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO J. 1994, 13: 5679-5688.PubMedPubMed Central
- Mattaj IW: RNA processing. Splicing in space. Nature. 1994, 372: 727-728. 10.1038/372727a0.PubMedView Article
- Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, Bell JC, Duncan PI: The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J. 1996, 15: 265-275.PubMedPubMed Central
- Okamoto Y, Onogi H, Honda R, Yasuda H, Wakabayashi T, Nimura Y, Hagiwara M: cdc2 kinase-mediated phosphorylation of splicing factor SF2/ASF. Biochem Biophys Res Commun. 1998, 249: 872-878. 10.1006/bbrc.1998.9247.PubMedView Article
- Soret J, Tazi J: Phosphorylation-dependent control of the pre-mRNA splicing machinery. Prog Mol Subcell Biol. 2003, 31: 89-126.PubMedView Article
- Schaal TD, Maniatis T: Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA. Mol Cell Biol. 1999, 19: 261-273.PubMedPubMed CentralView Article
- Fairbrother WG, Yeh RF, Sharp PA, Burge CB: Predictive identification of exonic splicing enhancers in human genes. Science. 2002, 297: 1007-1013. 10.1126/science.1073774.PubMedView Article
- Shen H, Kan JL, Green MR: Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly. Mol Cell. 2004, 13: 367-376. 10.1016/S1097-2765(04)00025-5.PubMedView Article
- Shen H, Green MR: A pathway of sequential arginine-serine-rich domain-splicing signal interactions during mammalian spliceosome assembly. Mol Cell. 2004, 16: 363-373. 10.1016/j.molcel.2004.10.021.PubMedView Article
- Hertel KJ, Lynch KW, Maniatis T: Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol. 1997, 9: 350-357. 10.1016/S0955-0674(97)80007-5.PubMedView Article
- Lam BJ, Hertel KJ: A general role for splicing enhancers in exon definition. RNA. 2002, 8: 1233-1241. 10.1017/S1355838202028030.PubMedPubMed CentralView Article
- Graveley BR, Hertel KJ, Maniatis T: A systematic analysis of the factors that determine the strength of pre- mRNA splicing enhancers. EMBO J. 1998, 17: 6747-6756. 10.1093/emboj/17.22.6747.PubMedPubMed CentralView Article
- Hertel KJ, Maniatis T: Serine-arginine (SR)-rich splicing factors have an exon-independent function in pre-mRNA splicing. Proc Natl Acad Sci USA. 1999, 96: 2651-2655. 10.1073/pnas.96.6.2651.PubMedPubMed CentralView Article
- Kanopka A, Muhlemann O, Akusjarvi G: Inhibition by SR proteins of splicing of a regulated adenovirus pre- mRNA. Nature. 1996, 381: 535-538. 10.1038/381535a0.PubMedView Article
- Ibrahim EC, Schaal TD, Hertel KJ, Reed R, Maniatis T: Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers. Proc Natl Acad Sci USA. 2005, 102: 5002-5007. 10.1073/pnas.0500543102.PubMedPubMed CentralView Article
- Cáceres JF, Screaton GR, Krainer AR: A specific subset of Sr proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev. 1998, 12: 55-66. 10.1101/gad.12.1.55.PubMedPubMed CentralView Article
- Huang Y, Steitz JA: Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol Cell. 2001, 7: 899-905. 10.1016/S1097-2765(01)00233-7.PubMedView Article
- Lee MS, Henry M, Silver PA: A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. Genes Dev. 1996, 10: 1233-1246. 10.1101/gad.10.10.1233.PubMedView Article
- Gilbert W, Siebel CW, Guthrie C: Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation. RNA. 2001, 7: 302-313. 10.1017/S1355838201002369.PubMedPubMed CentralView Article
- Blencowe BJ, Nickerson JA, Issner R, Penman S, Sharp PA: Association of nuclear matrix antigens with exon-containing splicing complexes. J Cell Biol. 1994, 127: 593-607. 10.1083/jcb.127.3.593.PubMedView Article
- Le Hir H, Moore MJ, Maquat LE: Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions. Genes Dev. 2000, 14: 1098-1108.PubMedPubMed Central
- Hautbergue GM, Hung ML, Golovanov AP, Lian LY, Wilson SA: Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP. Proc Natl Acad Sci USA. 2008, 105: 5154-5159. 10.1073/pnas.0709167105.PubMedPubMed CentralView Article
- Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR: The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol. 2007, 14: 185-193. 10.1038/nsmb1209.PubMedPubMed CentralView Article
- Sanford JR, Gray NK, Beckmann K, Caceres JF: A novel role for shuttling SR proteins in mRNA translation. Genes Dev. 2004, 18: 755-768. 10.1101/gad.286404.PubMedPubMed CentralView Article
- Michlewski G, Sanford JR, Caceres JF: The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Mol Cell. 2008, 30: 179-189. 10.1016/j.molcel.2008.03.013.PubMedView Article
- Bedard KM, Daijogo S, Semler BL: A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation. EMBO J. 2007, 26: 459-467. 10.1038/sj.emboj.7601494.PubMedPubMed CentralView Article
- Swartz JE, Bor YC, Misawa Y, Rekosh D, Hammarskjold ML: The shuttling SR protein 9G8 plays a role in translation of unspliced mRNA containing a constitutive transport element. J Biol Chem. 2007, 282: 19844-19853. 10.1074/jbc.M701660200.PubMedView Article
- Jenuwein T, Allis CD: Translating the histone code. Science. 2001, 293: 1074-1080. 10.1126/science.1063127.PubMedView Article
- Chasin LA: Searching for splicing motifs. Adv Exp Med Biol. 2007, 623: 85-106.PubMedView Article
- Hertel KJ: Combinatorial control of exon recognition. J Biol Chem. 2008, 283: 1211-1215. 10.1074/jbc.R700035200.PubMedView Article
- Faustino NA, Cooper TA: Pre-mRNA splicing and human disease. Genes Dev. 2003, 17: 419-437. 10.1101/gad.1048803.PubMedView Article
- Humphrey W, Dalke A, Schulten K: VMD: visual molecular dynamics. J Mol Graph. 1996, 14: 27-38.View Article
- Graveley BR, Hertel KJ: SR proteins. Encyclopedia of Life Sciences. 2005, Chichester: John Wiley & Sons, doi:10.1038/npg.els.0005039