Staufen (protein)

Maternal effect protein staufen
Identifiers
OrganismDrosophila melanogaster
Symbolstau
Entrez37065
OrthologsNCBI: entry; OMA: entry
PDB5CFF
RefSeq (mRNA)NM_057403
RefSeq (Prot)NP_476751.1
UniProtP25159
Other data
Chromosome2R: 18.12 - 18.13 Mb
Search for
StructuresSwiss-model
DomainsInterPro

Staufen is a protein product of a maternally expressed gene first identified in Drosophila melanogaster. The protein has been implicated in helping regulate genes important in determination of gradients that set up the anterior posterior axis such as bicoid and oskar. Staufen proteins, abbreviated Stau, are necessary for cell localization during the oogenesis and zygotic development.[1] It is involved in targeting of the messenger RNA encoding these genes to the correct pole of the egg cell.[2][3]

Human homologs of this protein include Staufen1 (STAU1) and Staufen2 STAU2.

Origin of the name

It was observed that Staufen mutants in Drosophila melanogaster failed to produce developing embryos. Therefore, the name "Staufen" comes after the Staufen dynasty, where all male offspring for several reasons died before reproducing.[4]

Forms

Staufen proteins are categorized under a family of double stranded RNA-binding proteins.[5] Many homologs of Staufen proteins exist depending on the organism. The mammalian homologs of Staufen include STAU1 and STAU2.[6] The gene encoding the STAU1 protein is found along the long arm of chromosome 20, while the gene encoding STAU2 is found on chromosome 8.[7] These proteins are identified by the presence of double-stranded RNA binding domains (dsRNA- binding domains), which functions to bind the protein to double-stranded secondary structure RNAs.[8] These two orthologues are produced in several different isoforms following pre mRNA splicing.[6] STAU1 is predominantly expressed in most cell types, while STAU2 is conserved the brain, with low level expression in other cell tissues.[6]

Localization of Staufen (Stau:GFP) in Drosophila stage 9 oocytes (white arrow).

Functions

Staufen-mediated mRNA decay.[9]

Staufen proteins are encoded and produced very early in oogenesis. At the primary stages of oogenesis, Staufen mRNA is evenly dispersed throughout the cytoplasm of the cell.[10] As the oocyte develops, the proteins condense at the anterior margins and the posterior pole of the egg cell.[10] In Drosophila the proteins are necessary for the translating and transporting oskar mRNA to the posterior pole of the oocyte.[7] Similarly Staufen proteins are also part of a multistep process that localizes Bicoid mRNA to the anterior end of the early embryo, and these proteins are also responsible for asymmetric dispersion of prospero mRNA as the embryonic neuroblast divides.[7][11]

In mammals, the STAU proteins contain a microtubule-binding domain, giving the protein the capability to bind to Tubulin. Research has also shown that these proteins maintain an association with the Rough endoplasmic reticulum (RER), suggesting that transport of mRNA through the use of Staufen proteins is facilitated via the microtubule network to the rough endoplasmic reticulum.[8]

Staufen is also known to induce Staufen-mediated mRNA decay (SMD). SMD occurs when Staufen protein binds to an mRNA and recruits SMD factors (i.e. UPF1, UPF2) that degrade the RNA molecule bound to Staufen.[12][9][13] SMD potently affects metabolism because it is reported to involve gene expression in more than 1000 mRNA transcripts.[14] SMD is reported to be a stepwise process: 1) two Staufen protein particles bind target mRNA by their double-stranded RNA binding domain (dsRBD) 3 and 4, 2) the two Staufen particles dimerizes by establishing non-covalent interactions between their Staufen-swapping motif (SSM) and dsRBD5 located in their C' termini, 3) this dimerized Staufen complex is recognized by SMD factors (i.e. UPF1, UPF2).[9][13] It was reported that, upon SSM deletion, Staufen particles bind to target mRNA but fail to dimerize and form a non-dimerized Staufen complex. This complex inhibits SMD.[9]

References

  1. ↑ "Society for Developmental Biology | Home". www.sdbonline.org. Retrieved 2022-05-03.
  2. ↑ Martin KC, Ephrussi A (February 2009). "mRNA Localization: Gene Expression in the Spatial Dimension". Cell. 136 (4): 719–730. Bibcode:2009Cell..136..719M. doi:10.1016/j.cell.2009.01.044. PMC 2819924. PMID 19239891.
  3. ↑ Houchmandzadeh B, Wieschaus E, Leibler S (February 2002). "Establishment of developmental precision and proportions in the early Drosophila embryo". Nature. 415 (6873): 798–802. Bibcode:2002Natur.415..798H. doi:10.1038/415798a. PMID 11845210. S2CID 4386630.
  4. ↑ Park E, Maquat LE (July 2013). "Staufen-mediated mRNA decay". WIREs RNA. 4 (4): 423–435. doi:10.1002/wrna.1168. ISSN 1757-7004. PMC 3711692. PMID 23681777.
  5. ↑ Almasi S, Jasmin BJ (December 2021). "The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events". Cellular and Molecular Life Sciences. 78 (23): 7145–7160. doi:10.1007/s00018-021-03965-w. PMC 8629789. PMID 34633481.
  6. 1 2 3 Heraud-Farlow JE, Kiebler MA (September 2014). "The multifunctional Staufen proteins: conserved roles from neurogenesis to synaptic plasticity". Trends in Neurosciences. 37 (9): 470–479. doi:10.1016/j.tins.2014.05.009. PMC 4156307. PMID 25012293.
  7. 1 2 3 Laver JD, Li X, Ancevicius K, Westwood JT, Smibert CA, Morris QD, et al. (November 2013). "Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity". Nucleic Acids Research. 41 (20): 9438–9460. doi:10.1093/nar/gkt702. PMC 3814352. PMID 23945942.
  8. 1 2 "STAU1 staufen double-stranded RNA binding protein 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-05-03.
  9. 1 2 3 4 Tripepi A, Shakoor H, Zlobina M, Klumpler T, Kubíčková M, Houser J, et al. (July 2026). "Staufen-swapping motif is crucial for Staufen dimerization, structure, and Staufen-mediated mRNA decay". Protein Science. 35 (7) e70669. doi:10.1002/pro.70669. PMC 13270411. PMID 42300088.
  10. 1 2 "Staufen". www.sdbonline.org. Retrieved 2022-05-03.
  11. ↑ "Staufen". www.sdbonline.org. Retrieved 2022-04-27.
  12. ↑ Gowravaram M, Schwarz J, Khilji SK, Urlaub H, Chakrabarti S (November 2019). "Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP". Nature Communications. 10 (1) 5054. Bibcode:2019NatCo..10.5054G. doi:10.1038/s41467-019-13080-x. PMC 6838198. PMID 31699982.
  13. 1 2 Gleghorn ML, Gong C, Kielkopf CL, Maquat LE (April 2013). "Staufen1 dimerizes through a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay". Nature Structural & Molecular Biology. 20 (4): 515–524. doi:10.1038/nsmb.2528. PMC 4096160. PMID 23524536.
  14. ↑ Chakrabarti AM, Iosub IA, Lee FC, Ule J, Luscombe NM (May 2023). "A computationally-enhanced hiCLIP atlas reveals Staufen1-RNA binding features and links 3' UTR structure to RNA metabolism". Nucleic Acids Research. 51 (8): 3573–3589. doi:10.1093/nar/gkad221. PMC 10164587. PMID 37013995.
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