Alternative titles; symbols
HGNC Approved Gene Symbol: SLBP
Cytogenetic location: 4p16.3 Genomic coordinates (GRCh38): 4:1,692,731-1,712,319 (from NCBI)
The stem-loop binding protein (SLBP), also known as hairpin binding protein, specifically recognizes the conserved stem loop present on metazoan replication-dependent histone mRNAs to regulate histone mRNA metabolism and is also required for the export, stability, and translation of mature mRNAs (summary by Tan et al., 2013).
Metazoan replication-dependent histone mRNAs do not have poly(A) tails but end instead in a highly conserved 26-bp sequence that contains a stem-loop structure. This structure is required for posttranscriptional processing of histone mRNA and is involved in histone RNA metabolism. Hairpin binding protein (HBP), also called stem-loop binding protein, has been shown to bind the stem-loop structure of histone mRNA. Using the yeast 3-hybrid system, Wang et al. (1996) and Martin et al. (1997) independently cloned a cDNA encoding HBP. HBP is a 270-amino acid protein that does not contain any previously described RNA-binding domains. It shares 89% and 60% sequence identity with mouse and frog Hbp, respectively. The calculated mass of 31 kD for HBP is lower than the 43 to 45 kD estimated by SDS-PAGE, and Wang et al. (1996) attributed this discrepancy to an anomalous mobility of HBP on SDS-PAGE. By Northern blot analysis, Martin et al. (1997) detected an approximately 2-kb HBP transcript in all human tissues examined.
Wang et al. (1996) showed that HBP is the major protein in nuclear and polyribosomal extracts that specifically binds the histone mRNA stem-loop structure. They mapped the novel RNA-binding domain of HBP to a 73-amino acid region. Wang et al. (1996) and Martin et al. (1997) demonstrated that HBP is required for efficient histone pre-mRNA processing, and predicted that it is involved in many aspects of histone RNA metabolism.
Martin et al. (1997) found that the HBP gene has 8 exons covering approximately 19.5 kb.
Martin et al. (1997) found by nucleotide sequence comparisons that the genomic region of HBP had previously been sequenced during the search for the Huntington disease locus on chromosome 4p16.3.
Crystal Structure
Tan et al. (2013) reported the crystal structure of a ternary complex of human SLBP RNA-binding domain, human 3-prime-HEXO (ERI1; 608739), and a 26-nucleotide stem-loop RNA. Only 1 base of the stem-loop is recognized specifically by the SLBP, and the 2 proteins primarily recognize the shape of the RNA. SLBP and 3-prime-HEXO have no direct contact with each other, and induced structural changes in the loop of the stem-loop mediate their cooperative binding. The 3-prime flanking sequence is positioned in the 3-prime-HEXO active site, but the ternary complex limits the extent of the trimming.
Martin, F., Schaller, A., Eglite, S., Schumperli, D., Muller, B. The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein. EMBO J. 16: 769-778, 1997. [PubMed: 9049306] [Full Text: https://doi.org/10.1093/emboj/16.4.769]
Tan, D., Marzluff, W. F., Dominski, Z., Tong, L. Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3-prime-hExo ternary complex. Science 339: 318-321, 2013. [PubMed: 23329046] [Full Text: https://doi.org/10.1126/science.1228705]
Wang, Z.-F., Whitfield, M. L., Ingledue, T. C., III, Dominski, Z., Marzluff, W. F. The protein that binds the 3-prime end of histone mRNA: a novel RNA-binding protein required for histone pre-mRNA processing. Genes Dev. 10: 3028-3040, 1996. [PubMed: 8957003] [Full Text: https://doi.org/10.1101/gad.10.23.3028]