Figure 1. Organization of the human genes that encode SR proteins. The exon–intron organization of each human SR protein gene is shown. Noncoding portions of each exon are represented by white boxes, coding portions of exons are indicated by black boxes. Alternatively spliced exons are indicated in gray. The splicing of the alternative exons is autoregulated by the SR protein encoded by the gene. The exons and introns for each gene are drawn to scale and the size of each gene is indicated.

Figure 2. The human SR protein family. The structural organization of the nine human SR proteins is shown. RRM: RNA recognition motif; RRMH: RRM homology; Zn: zinc-knuckle; RS: arginine/serine-rich domain.

Figure 3. Exon-dependent functions of SR proteins. (a) ESE-bound SR proteins may function by activating upstream 3¢ splice sites. This can be achieved through recruitment of the general splicing factor U2AF, through interactions with the splicing coactivator SRm160, or by antagonizing the activity of splicing inhibitors. (b) Alternative 5¢ splice sites may be activated on the recruitment of U1 snRNP by ESE-bound SR proteins. (c) SR proteins may function in constitutive splicing by simultaneously interacting with U2AF bound to the upstream 3¢ splice site and U1 snRNP bound to the downstream 5¢ splice site. Py: pyrimidine tract.

Figure 4. Exon-independent functions of SR proteins. SR proteins have two exon-independent functions. First, SR proteins facilitate splice-site pairing by simultaneously interacting with U1 snRNP and U2AF across the intron. Second, SR proteins in the partially assembled spliceosome are involved in recruiting the U4/U6•U5 tri-snRNP.

Figure 5. Models of mRNA export. (a) Intronless mRNAs such as H2a contain high-affinity binding sites (black box) for SR proteins that shuttle continuously between the nucleus and the cytoplasm. Association of shuttling SR proteins with the intronless mRNA leads to nuclear export via an unknown pathway. (b) Before splicing, nascent pre-mRNAs are coated by hnRNPs (heterogeneous nuclear ribonucleoproteins). During spliceosomal assembly, SR proteins bind to each exon with sufficient affinity to replace hnRNPs effectively. During intron removal, conserved export factors, in particular ALY/REF, are recruited to the exons. Because of their association with exonic sequences throughout the splicing cycle, SR proteins may assist in linking pre-mRNA splicing to mRNA export either directly by interacting with the export machinery or indirectly by inhibiting the association of nuclear retention factors such as hnRNPs with the mRNA. The spliced mRNA is then exported from the nucleus via a pathway involving TAP/p15, Gle, Gle2 or Dbp5 (nuclear export factors).