The SF3b complex: splicing and beyond
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Cellular and Molecular Life Sciences
REVIEW
The SF3b complex: splicing and beyond Chengfu Sun1 Received: 21 January 2020 / Revised: 13 February 2020 / Accepted: 20 February 2020 © The Author(s) 2020
Abstract The SF3b complex is an intrinsic component of the functional U2 small nuclear ribonucleoprotein (snRNP). As U2 snRNP enters nuclear pre-mRNA splicing, SF3b plays key roles in recognizing the branch point sequence (BPS) and facilitating spliceosome assembly and activation. Since the discovery of SF3b, substantial progress has been made in elucidating its molecular mechanism during splicing. In addition, numerous recent studies indicate that SF3b and its components are engaged in various molecular and cellular events that are beyond the canonical role in splicing. This review summarizes the current knowledge on the SF3b complex and highlights its multiple roles in splicing and beyond. Keywords Intron · Branch site adenosine (BS-a) · Cancer · Modification · Nonsplicing · U2-snRNP-dependent
Introduction
Composition and structure
Introns were discovered in the late 1970s [1, 2]. The splicing of introns from nuclear precursors of message RNA (premRNA) is executed by the spliceosome, a ribonucleoprotein (RNP) apparatus that first surfaced in the literature in 1985 [3–5]. Since the discovery of this splicing machinery, characterization of its biochemical composition and catalytic properties has flourished in the splicing field. Early applications of chromatographic fractionation procedures in HeLa cells produced various protein complexes, designated SF factors (SF1 to SF4), that are required for splicing [6]. One of these protein complexes, SF3, was further shown to contain two subcomplexes, SF3a and SF3b [7]. Although the name for SF3b first appeared in 1993, studies on its composition and function, as will be discussed in subsequent sections in this review, were already ongoing at that time. Excellent reviews have recently been published on the structures and functions of U2 small nuclear ribonucleoprotein (snRNP) and SF3b1 in splicing [8, 9]. In this review, I focus on the SF3b complex and discuss its roles in splicing as well as multiple emerging nonsplicing roles.
Characterization of the purified SF3b complex indicated that it consists of seven proteins with a molecular size ranging from 10 to 155 kDa [10–12] (Fig. 1a). Due to methodological differences in identifying SF3b components in human and yeast, a number of names have been designated for these proteins across different species. In this review, I will use SF3b1-7 for consistency and clarity (Fig. 1a). Seven SF3b components have been shown to contain distinct domains (Fig. 1b). SF3b1 is the largest protein in the SF3b complex, with a notable region containing 20 tandem repeats termed the HEAT domain. This region was originally found in and named after Huntingtin, EF3, PP2A, and TOR1 [13, 14]. In addition, SF3b1 harbors a stretch of U2AF ligand motifs (ULMs) at its N-terminus, which can specifically interact with the U2AF homology motif (UHM) found i
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