SLBP

Histone RNA hairpin-binding protein or stem-loop binding protein (SLBP) is a protein that in humans is encoded by the SLBP gene.[5][6][7]

SLBP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSLBP, HBP, stem-loop binding protein
External IDsOMIM: 602422 MGI: 108402 HomoloGene: 31389 GeneCards: SLBP
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4p16.3Start1,692,731 bp[1]
End1,712,344 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

7884

20492

Ensembl

ENSG00000163950

ENSMUSG00000004642

UniProt

Q14493
Q53XR2

P97440

RefSeq (mRNA)

NM_001306074
NM_001306075
NM_006527

NM_001289724
NM_001289725
NM_009193

RefSeq (protein)

NP_001293003
NP_001293004
NP_006518
NP_006518.1

NP_001276653
NP_001276654
NP_033219

Location (UCSC)Chr 4: 1.69 – 1.71 MbChr 5: 33.63 – 33.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Species distribution

SLBP has been cloned from humans, C. elegans, D. melanogaster, X. laevis, and sea urchins. The full length human protein has 270 amino acids (31 kDa) with a centrally located RNA binding domain (RBD). The 75 amino acid RBD is well conserved across species, however the remainder of SLBP is highly divergent in most organisms and not homologous to any other protein in the eukaryotic genomes.

Function

This gene encodes a protein that binds to the histone 3' UTR stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by a single endonucleolytic cleavage event downstream of the stem-loop. The stem-loop structure is essential for efficient processing of the histone pre-mRNA but this structure also controls the transport, translation and stability of histone mRNAs. SLBP expression is regulated during S-phase of the cell cycle, increasing more than 10-fold during the latter part of G1.

All SLBP proteins are capable of forming a highly stable complex with histone stem-loop RNA. Complex formation with the histone mRNA stem-loop is achieved by a novel three-helix bundle fold. SLBP proteins also recognize the tetraloop structure of the histone hairpin, the base of the stem, and the 5' flanking region. The crystal structure of human SLBP in complex with the stem-loop RNA as well as the exonuclease Eri1 reveals that the Arg181 residue of SLBP specifically interacts with the second guanine base in the RNA stem.[8] The rest of the protein is intrinsically disordered in fruit-flies as well as in humans. A unique feature of the SLBP RBD is that it is phosphorylated in its RNA binding domain at the Thr171 residue. The SLBP RBD also undergoes proline isomerization about this sequence and is a substrate for the prolyl isomerase Pin1. The N-terminal domain of human SLBP is required for translation activation of histone mRNAs via its interaction with SLIP1. SLBP also interacts with the CBP80 associated protein CTIF to facilitate rapid degradation of histone mRNAs. SLBP is a phosphoprotein and besides T171, it is also phosphorylated at Ser7, Ser20, Ser23, Thr60, Thr61 in mammalian cells. The phosphorylation at Thr60 is mediated by CK2 and Thr61 is by Cyclin A/Cdk1.[7]

References

  1. GRCh38: Ensembl release 89: ENSG00000163950 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000004642 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Martin F, Schaller A, Eglite S, Schumperli D, Muller B (Mar 1997). "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 (4): 769–78. doi:10.1093/emboj/16.4.769. PMC 1169678. PMID 9049306.
  6. McCombie WR, Martin-Gallardo A, Gocayne JD, FitzGerald M, Dubnick M, Kelley JM, Castilla L, Liu LI, Wallace S, Trapp S (August 1992). "Expressed genes, Alu repeats and polymorphisms in cosmids sequenced from chromosome 4p16.3". Nature Genetics. 1 (5): 348–53. doi:10.1038/ng0892-348. PMID 1338771. S2CID 6716635.
  7. "Entrez Gene: SLBP stem-loop (histone) binding protein".
  8. Dazhi Tan; William F. Marzluff; Zbigniew Dominski; Liang Tong (Jan 2013). "Structure of Histone mRNA Stem-Loop, Human Stem-Loop Binding Protein, and 3′hExo Ternary Complex". Science. 339 (6117): 318–321. doi:10.1126/science.1228705. PMC 3552377. PMID 23329046.

Further reading

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