SLBP

SLBP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KJM, 4QOZ
Identifiers
Aliases	SLBP , HBP, stem-loop binding protein
External IDs	OMIM: 602422 MGI: 108402 HomoloGene: 31389 GeneCards: SLBP
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4p16.3 Start 1,692,731 bp [1] End 1,712,344 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 B2 Start 33,634,952 bp [2] End 33,652,574 bp [2]
RNA expression pattern Bgee Top expressed in testicle thymus bone marrow material anatomical entity caudate nucleus kidney lymph node retinal pigment epithelium hypothalamus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function histone pre-mRNA DCP binding histone pre-mRNA stem-loop binding GO:0001948 protein binding mRNA binding RNA binding identical protein binding Cellular component cytoplasm histone pre-mRNA 3'end processing complex nucleoplasm nucleus nucleolus cytosol ribonucleoprotein complex Biological process termination of RNA polymerase II transcription mRNA transport mRNA 3'-end processing by stem-loop binding and cleavage mRNA processing mRNA export from nucleus nuclear DNA replication histone mRNA metabolic process cell cycle phase transition Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	Chr 5: 33.63 – 33.65 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]}

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

• Choe J, Mi Kim K, Park S, Kyung Lee Y, Song O-K, Kim MK, Lee BG, Song HK, Kim YK (2013). "Rapid degradation of replication-dependent histone mRNAs largely occurs on mRNAs bound by nuclear cap-binding proteins 80 and 20". Nucleic Acids Research. 41 (2): 1307–1318. doi:10.1093/nar/gks1196. PMC   3553978 . PMID   23234701.
• Bansal N, Zhang M, Bhaskar A, Itotia P, Lee E, Shlyakhtenko LS, Lam TT, Fritz A, Berezney R, Lyubchenko YL, Stafford WF, Thapar R (January 2013). "Assembly of the SLIP1-SLBP complex on histone mRNA requires heterodimerization and sequential binding of SLBP followed by SLIP1". Biochemistry. 52 (3): 520–536. doi:10.1021/bi301074r. PMC   3580866 . PMID   23286197.
• Martin L, Meier M, Lyons SM, Sit RV, Marzluff WF, Quake SR, Chang HY (December 2012). "Systematic reconstruction of RNA functional motifs with high-throughput microfluidics". Nature Methods. 9 (12): 1192–4. doi:10.1038/nmeth.2225. PMC   3863600 . PMID   23142872.
• Krishnan N, Lam TT, Fritz A, Rempinski D, O'Loughlin K, Minderman H, Berezney R, Marzluff WF, Thapar R (November 2012). "The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination". Mol. Cell. Biol. 32 (21): 4306–22. doi:10.1128/MCB.00382-12. PMC   3486140 . PMID   22907757.
• Zhang M, Lam TT, Tonelli M, Marzluff WF, Thapar R (April 2012). "Interaction of the histone mRNA hairpin with stem-loop binding protein (SLBP) and regulation of the SLBP-RNA complex by phosphorylation and proline isomerization". Biochemistry. 51 (15): 3215–31. doi:10.1021/bi2018255. PMC   3328597 . PMID   22439849.
• Borchers CH, Thapar R, Petrotchenko EV, Torres MP, Speir JP, Easterling M, Dominski Z, Marzluff WF (February 2006). "Combined top-down and bottom-up proteomics identifies a phosphorylation site in stem-loop-binding proteins that contributes to high-affinity RNA binding". Proc. Natl. Acad. Sci. U.S.A. 103 (9): 3094–9. Bibcode:2006PNAS..103.3094B. doi: 10.1073/pnas.0511289103 . PMC   1413926 . PMID   16492733.
• Thapar R, Marzluff WF, Redinbo MR (July 2004). "Electrostatic contribution of serine phosphorylation to the Drosophila SLBP--histone mRNA complex". Biochemistry. 43 (29): 9401–12. doi:10.1021/bi036315j. PMID   15260483.
• Thapar R, Mueller GA, Marzluff WF (July 2004). "The N-terminal domain of the Drosophila histone mRNA binding protein, SLBP, is intrinsically disordered with nascent helical structure". Biochemistry. 43 (29): 9390–400. doi:10.1021/bi036314r. PMID   15260482.
• Wang ZF, Whitfield ML, Ingledue TC, Dominski Z, Marzluff WF (December 1996). "The protein that binds the 3' end of histone mRNA: a novel RNA-binding protein required for histone pre-mRNA processing". Genes Dev. 10 (23): 3028–40. doi: 10.1101/gad.10.23.3028 . PMID   8957003.
• Dominski Z, Zheng LX, Sanchez R, Marzluff WF (May 1999). "Stem-loop binding protein facilitates 3'-end formation by stabilizing U7 snRNP binding to histone pre-mRNA". Mol. Cell. Biol. 19 (5): 3561–70. doi:10.1128/mcb.19.5.3561. PMC   84148 . PMID   10207079.
• Whitfield ML, Zheng LX, Baldwin A, Ohta T, Hurt MM, Marzluff WF (June 2000). "Stem-loop binding protein, the protein that binds the 3' end of histone mRNA, is cell cycle regulated by both translational and posttranslational mechanisms". Mol. Cell. Biol. 20 (12): 4188–98. doi:10.1128/MCB.20.12.4188-4198.2000. PMC   85788 . PMID   10825184.
• Dominski Z, Erkmann JA, Greenland JA, Marzluff WF (March 2001). "Mutations in the RNA binding domain of stem-loop binding protein define separable requirements for RNA binding and for histone pre-mRNA processing". Mol. Cell. Biol. 21 (6): 2008–17. doi:10.1128/MCB.21.6.2008-2017.2001. PMC   86798 . PMID   11238936.
• Allard P, Champigny MJ, Skoggard S, Erkmann JA, Whitfield ML, Marzluff WF, Clarke HJ (December 2002). "Stem-loop binding protein accumulates during oocyte maturation and is not cell-cycle-regulated in the early mouse embryo". J. Cell Sci. 115 (Pt 23): 4577–86. doi:10.1242/jcs.00132. PMC   5115915 . PMID   12415002.
• Zheng L, Dominski Z, Yang XC, Elms P, Raska CS, Borchers CH, Marzluff WF (March 2003). "Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase". Mol. Cell. Biol. 23 (5): 1590–601. doi:10.1128/MCB.23.5.1590-1601.2003. PMC   151715 . PMID   12588979.
• Koseoglu MM, Graves LM, Marzluff WF (July 2008). "Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase". Mol. Cell. Biol. 28 (14): 4469–79. doi:10.1128/MCB.01416-07. PMC   2447125 . PMID   18490441.
• Sànchez R, Marzluff WF (October 2002). "The stem-loop binding protein is required for efficient translation of histone mRNA in vivo and in vitro". Mol. Cell. Biol. 22 (20): 7093–104. doi:10.1128/mcb.22.20.7093-7104.2002. PMC   139811 . PMID   12242288.
• Zhao X, McKillop-Smith S, Müller B (December 2004). "The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells". J. Cell Sci. 117 (Pt 25): 6043–51. doi: 10.1242/jcs.01523 . PMID   15546920.
• Erkmann JA, Wagner EJ, Dong J, Zhang Y, Kutay U, Marzluff WF (June 2005). "Nuclear import of the stem-loop binding protein and localization during the cell cycle". Mol. Biol. Cell. 16 (6): 2960–71. doi:10.1091/mbc.E04-11-1023. PMC   1142439 . PMID   15829567.