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The Branchpoint Binding Protein

In and Out of the Spliceosome Cycle
  • Brian C. Rymond
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 693)

Abstract

The Saccharomyces cerevisiae branchpoint binding protein (BBP) is a 53 kDa pre-mRNA processing factor with characteristic STAR/GSG protein organization. This includes a central RNA binding site composed of an extended Type I KH domain with an adjacent QUA2 motif. Downstream of KH-QUA2 are two CCHC-type zinc knuckles and a proline-rich C-terminal interaction domain (Fig. 1A). The QUA1 homodimerization motif found upstream of the KH-QUA2 sequence in other STAR/GSG family members is absent in BBP and replaced by a site for the phylogenetically conserved binding partner, Mud2/U2AF65. BBP’s name reflects the fact that it binds the conserved RNA sequence, UACUAAC, called the branchpoint motif found near the 3′ end of yeast introns. This sequence contains the catalytic adenosine (underlined) which directs the first RNA transesterification reaction in splicing chemistry. BBP recruitment to the branchpoint initiates a series of spliceosomal subunit addition and rearrangement events that ultimately configures the active site of this enzyme.1 The mammalian homolog, ZF M1/ZNF162/D11S636/SF1 (henceforth, SF1), was first identified in a screen for genes associated with Type 1 multiple endocrine neoplasia2 and was subsequently shown to act similarly to BBP in mammalian splicing.3,4 BBP/SF1 is essential for viability in organisms spanning the evolutionary spectrum from yeast to Caenorhabditis elegans to mice. In addition, mice heterozygous for a SF1 knockout allele show enhanced susceptibility to azoxymethane-induced colon tumorigenesis5 adding BBP/SF1 to the growing list of RNA processing factors implicated in genetic disease.6 Summarized below is our current understanding of BBP structure and its proposed multifaceted contribution to mRNA biogenesis and function. Reference to SF1 will be made to fill gaps in our understanding of BBP and to highlight areas of clear similarity or difference between yeast and mammals.
Figure 1

Domain organization of the BBP/SF1 splicing factor. A) Schematic representation of BBP. Indicated are the ULM domain-containing region that mediates Mud2 association (Heterodimerization); the RNA binding element (KH_QUA2), two CCHC zinc knuckles (Zn) and the positions conforming to the Smy2 binding site, PPG{F/I/L/M/V}. The Smy2 sequences overlap a clathrin adaptor appendage domain that has not been scored for function in BBP. B) Alignment of the yeast BBP and human SF1 proteins using Blossom 62 matrix with identities shaded black and conserved residues shaded gray. Shown above BBP is the ULM sub-sequence critical to the SF1/U2AF65 interaction, the location of the KIS phosphorylation motif and the βααββ αα secondary structures (thick dashed line) of the KH-QUA2 motif. Also shown are the two loop sequences that contribute to the RNA binding channel (^) and the six Smy2 binding sites (*).

Keywords

Splice Factor Nuclear Retention Star Protein Spliceosome Assembly snRNP Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Brian C. Rymond
    • 1
  1. 1.Biology DepartmentUniversity of KentuckyLexingtonUSA

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