SR proteins and galectins: what's in a name?

Abstract

Although members of the serine (S)- and arginine (R)-rich splicing factor family (SR proteins) were initially purified on the basis of their splicing activity in the nucleus, there is recent documentation that they exhibit carbohydrate-binding activity at the cell surface. In contrast, galectins were isolated on the basis of their saccharide-binding activity and cell surface localization. Surprisingly, however, two members (galectin-1 and galectin-3) can be found in association with nuclear ribonucleoprotein complexes including the spliceosome and, using a cell-free assay, have been shown to be required splicing factors. Thus, despite the difference in terms of their original points of interest, it now appears that members of the two protein families share four key properties: (a) nuclear and cytoplasmic distribution; (b) pre-mRNA splicing activity; (c) carbohydrate-binding activity; and (d) cell surface localization in specific cells. These findings provoke stimulating questions regarding the relationship between splicing factors in the nucleus and carbohydrate-binding proteins at the cell surface.

Fig. 1

Diagram illustrating the domain content and organization of the polypeptides of the SR splicing factor family and the galectin family. (A) The seven canonical members of the SR protein family are arranged in the order of the common nomenclature, Sfrs1 through Sfrs7. RRM, RNA recognition motif; RS, domain rich in arginine and serine dipeptides. (B) The 15 members of the galectin family are classified into three subfamilies, based on the number and arrangement of domains. CRD, carbohydrate recognition domain. Conserved amino acid residues in the CRD are highlighted. The amino terminal domain of galectin-3, the sole representative of the Chimera group, contains a repeating motif rich in proline and glycine residues. The single amino acid code is used; X denotes any amino acid

Fig. 2

Schematic comparison of the “initial” and the “emerging” views of the localization and activities of the SR splicing factor and the galectin protein families. (A) The SR proteins were initially identified as splicing factors in the nucleus. (B) It is now known that SR proteins are also found as components of mRNPs in the cytoplasm as well as cell-surface carbohydrate-binding proteins. (C) Galectins were initially studied as carbohydrate-binding proteins of the cell surface and extracellular matrix. (D) Galectins have now been localized in the nucleus, and at least two members of the family participate in pre-mRNA splicing. The possibility that cell surface galectin serves as a carbohydrate receptor is also raised in this depiction. RRM, RNA recognition motif; RS, domain rich in arginine and serine dipeptides; CRD, carbohydrate recognition domain; CHO, carbohydrate

Fig. 3

Diagram illustrating the association of SR splicing factor(s) and galectin(s) with snRNPs and with the pre-mRNA substrate in the assembly of the spliceosome. The pre-mRNA is shown on the left side as two rectangular exons joined by a single-line intron. The SR proteins, represented by Sfrs, can interact with the pre-mRNA via its RNA recognition motif. Galectin-3 (Gal3) can enter the splicing pathway through its association with U1 snRNP, highlighted at the top on the right side. The unmarked ovals represent other components of the splicing machinery. The left side highlights the fact that Sfrs and Gal3 are associated with the pre-mRNA substrate from the early commitment complex through the active C complex, and the final mature mRNA product. Both Sfrs and Gal3 are found as free polypeptides as well as being associated with multiple snRNPs in larger complexes outside of the spliceosome, as schematically illustrated on the right side