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SYNCRIP

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SYNCRIP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSYNCRIP, GRY-RBP, GRYRBP, HNRNPQ, HNRPQ1, NSAP1, PP68, hnRNP-Q, synaptotagmin binding cytoplasmic RNA interacting protein
External IDsOMIM: 616686; MGI: 1891690; HomoloGene: 4648; GeneCards: SYNCRIP; OMA:SYNCRIP - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10492

56403

Ensembl

ENSG00000135316

ENSMUSG00000032423

UniProt

O60506

Q7TMK9

RefSeq (mRNA)

NM_001284328
NM_019666
NM_019796
NM_001311113

RefSeq (protein)

NP_001271257
NP_001298042
NP_062640
NP_062770

Location (UCSC)Chr 6: 85.61 – 85.64 MbChr 9: 88.33 – 88.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as heterogeneous nuclear ribonucleoprotein (hnRNP) Q or NS1-associated protein-1 (NSAP-1), is a protein that in humans is encoded by the SYNCRIP gene.[5][6][7] As the name implies, SYNCRIP is localized predominantly in the cytoplasm.[8] It is evolutionarily conserved across eukaryotes and participates in several cellular and disease pathways, especially in neuronal and muscular development.[9] In humans, there are three isoforms, all of which are associated in vitro with pre-mRNAs, mRNA splicing intermediates, and mature mRNA-protein complexes, including mRNA turnover.[10]

Structure and function

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This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA).

SYNCRIP is made up of an N-terminal helix bundle known as the “acidic domain” (AcD), followed by three sequential RNA recognition motifs (RRMs) separated by short linkers, and an arginine-glycine-rich domain called the "RGG box" at the C-terminus. The RRMs play a role in RNA binding, while the AcD engages in protein-protein interactions (PPIs). The RGG box is involved in both RNA binding and in PPIs. The AcD is unique to SYNCRIP and its nuclear homolog hnRNP R, and is involved in interactions with APOBEC-1.[11] It is a self-folding, all-helical domain of five α-helices, containing a large hydrophobic cavity and a positively charged surface area as potential interaction sites in addition to negatively charged surface areas, with no structural homologs in any other known proteins.[11][12] The hydrophobic core is mostly made up of leucine residues, while the surface is made up of 15 acidic residues and 13 basic residues which together form a vast interaction network.[12] The AcD is linked to RRM1 by a unique α-β-β unit, creating an “extended RRM fold” mediated primarily by hydrophobic interactions.[12] The RGG box is an unstructured region containing numerous Arg-Gly-Gly repeats with fairly regular spacing. There are eight such repeats in SYNCRIP. This domain can bind proteins and RNA independently, even if the other binding domains are not present.[13] Although this domain is rich in arginine content, it does not have any arginine-rich clusters as might be observed in usual arginine-rich RBPs.[13]

Isoform 1 is a component of the apolipoprotein B (apoB) mRNA editosome complex, and it modulates the post-transcriptional C-to-U RNA editing of apoB mRNA through binding either to the apoB mRNA-editing enzyme catalytic peptide 1 (APOBEC-1), to the APOBEC-1 complementation factor (ACF), or directly to RNA itself.[6] Isoform 1 is also implicated with other RBPs in the cytoplasmic de-adenylation and translational and decay interplay of c-Fos mRNA mediated by the major coding-region determinant of instability (mCRD) domain.[14]

The function of isoform 2 is not as clearly understood.

Isoform 3 is involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins (SYTs).[8] This isoform is also a component of the gamma interferon (IFNγ)-activated inhibitor of translation (GAIT) complex in humans, which mediates IFNγ-induced transcript-selective translation inhibition in inflammation processes.[15] Upon IFN-γ activation, SYNCRIP assembles into the GAIT complex, which binds to stem-loop-containing GAIT elements in the 3’-untranslated region (3’- UTR) of diverse inflammatory mRNAs and suppresses their translation, but this seems to not be essential for the overall function of the GAIT complex.[15]

Interactions

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SYNCRIP has been shown to interact with ACF,[6][16] APOBEC1,[6] SYT7,[8] and SYT9.[8]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135316 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032423 – 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. ^ Harris CE, Boden RA, Astell CR (January 1999). "A novel heterogeneous nuclear ribonucleoprotein-like protein interacts with NS1 of the minute virus of mice". Journal of Virology. 73 (1): 72–80. doi:10.1128/JVI.73.1.72-80.1999. PMC 103810. PMID 9847309.
  6. ^ a b c d Lau PP, Chang BH, Chan L (April 2001). "Two-hybrid cloning identifies an RNA-binding protein, GRY-RBP, as a component of apobec-1 editosome". Biochemical and Biophysical Research Communications. 282 (4): 977–83. doi:10.1006/bbrc.2001.4679. PMID 11352648.
  7. ^ "Entrez Gene: SYNCRIP synaptotagmin binding, cytoplasmic RNA interacting protein".
  8. ^ a b c d Mizutani A, Fukuda M, Ibata K, Shiraishi Y, Mikoshiba K (March 2000). "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms". The Journal of Biological Chemistry. 275 (13): 9823–31. doi:10.1074/jbc.275.13.9823. PMID 10734137.
  9. ^ Chen Y, Chan J, Chen W, Li J, Sun M, Kannan GS, Mok YK, Yuan YA, Jobichen C (March 2020). "SYNCRIP, a new player in pri-let-7a processing". RNA. 26 (3): 290–305. doi:10.1261/rna.072959.119. PMC 7025501. PMID 31907208.
  10. ^ Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G (October 2001). "SMN interacts with a novel family of hnRNP and spliceosomal proteins". The EMBO Journal. 20 (19): 5443–52. doi:10.1093/emboj/20.19.5443. PMC 125643. PMID 11574476.
  11. ^ a b Beuck C, Williamson JR, Wüthrich K, Serrano P (August 2016). "The acidic domain is a unique structural feature of the splicing factor SYNCRIP". Protein Science. 25 (8): 1545–50. doi:10.1002/pro.2935. PMC 4972210. PMID 27081926.
  12. ^ a b c Hobor F, Dallmann A, Ball NJ, Cicchini C, Battistelli C, Ogrodowicz RW, Christodoulou E, Martin SR, Castello A, Tripodi M, Taylor IA, Ramos A (February 2018). "A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets". Nature Communications. 9 (1): 831. Bibcode:2018NatCo...9..831H. doi:10.1038/s41467-018-03182-3. PMC 5827114. PMID 29483512.
  13. ^ a b Kiledjian M, Dreyfuss G (1992). "Primary structure and binding activity of the hnRNP U protein: Binding RNA through RGG box". EMBO Journal. 11 (7): 2655–64. doi:10.1002/j.1460-2075.1992.tb05331.x. ISSN 0261-4189. PMC 556741. PMID 1628625.
  14. ^ Grosset C, Chen CY, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu AB (September 2000). "A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex". Cell. 103 (1): 29–40. doi:10.1016/S0092-8674(00)00102-1. PMID 11051545. S2CID 18135412.
  15. ^ a b Arif A, Chatterjee P, Moodt RA, Fox PL (October 2012). "Heterotrimeric GAIT Complex Drives Transcript-Selective Translation Inhibition in Murine Macrophages". Molecular and Cellular Biology. 32 (24): 5046–55. doi:10.1128/mcb.01168-12. PMC 3510535. PMID 23071094.
  16. ^ Blanc V, Navaratnam N, Henderson JO, Anant S, Kennedy S, Jarmuz A, Scott J, Davidson NO (March 2001). "Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing". The Journal of Biological Chemistry. 276 (13): 10272–83. doi:10.1074/jbc.M006435200. PMID 11134005.

Further reading

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