The branchpoint binding protein: In and out of the spliceosome cycle

Brian C. Rymond

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

8 Scopus citations


The Saccharomyces cerevisiae branchpoint binding protein (BBP) is a 53 kDa pre-mRNA processing factor with characteristic STARJ/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 STAPJGSG 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. 1The mammalian homolog, ZFM1/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. 3,4BBP/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. 6Summarized 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.

Original languageEnglish
Title of host publicationPost-Transcriptional Regulation by STAR Proteins
Subtitle of host publicationControl of RNA Metabolism in Development and Disease
EditorsTalila Volk, Karen Artzt
Number of pages19
StatePublished - 2010

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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