SYNCRIP

Last updated
SYNCRIP
Protein SYNCRIP PDB 2dgu.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SYNCRIP , GRY-RBP, GRYRBP, HNRNPQ, HNRPQ1, NSAP1, PP68, hnRNP-Q, synaptotagmin binding cytoplasmic RNA interacting protein
External IDs OMIM: 616686 MGI: 1891690 HomoloGene: 4648 GeneCards: SYNCRIP
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 Mb Chr 9: 88.33 – 88.36 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

Structure and function

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

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

Related Research Articles

RNA-binding proteins are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA recognition motif (RRM), dsRNA binding domain, zinc finger and others. They are cytoplasmic and nuclear proteins. However, since most mature RNA is exported from the nucleus relatively quickly, most RBPs in the nucleus exist as complexes of protein and pre-mRNA called heterogeneous ribonucleoprotein particles (hnRNPs). RBPs have crucial roles in various cellular processes such as: cellular function, transport and localization. They especially play a major role in post-transcriptional control of RNAs, such as: splicing, polyadenylation, mRNA stabilization, mRNA localization and translation. Eukaryotic cells express diverse RBPs with unique RNA-binding activity and protein–protein interaction. According to the Eukaryotic RBP Database (EuRBPDB), there are 2961 genes encoding RBPs in humans. During evolution, the diversity of RBPs greatly increased with the increase in the number of introns. Diversity enabled eukaryotic cells to utilize RNA exons in various arrangements, giving rise to a unique RNP (ribonucleoprotein) for each RNA. Although RBPs have a crucial role in post-transcriptional regulation in gene expression, relatively few RBPs have been studied systematically.It has now become clear that RNA–RBP interactions play important roles in many biological processes among organisms.

Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.

<span class="mw-page-title-main">Heterogeneous ribonucleoprotein particle</span>

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.

<span class="mw-page-title-main">Survival of motor neuron</span> Protein in animal cells

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

<span class="mw-page-title-main">HNRNPA1</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the HNRNPA1 gene. Mutations in hnRNP A1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy.

<span class="mw-page-title-main">HNRNPK</span> Human protein and coding gene

Heterogeneous nuclear ribonucleoprotein K is a protein that in humans is encoded by the HNRNPK gene. It is found in the cell nucleus that binds to pre-messenger RNA (mRNA) as a component of heterogeneous ribonucleoprotein particles. The simian homolog is known as protein H16. Both proteins bind to single-stranded DNA as well as to RNA and can stimulate the activity of RNA polymerase II, the protein responsible for most gene transcription. The relative affinities of the proteins for DNA and RNA vary with solution conditions and are inversely correlated, so that conditions promoting strong DNA binding result in weak RNA binding.

<span class="mw-page-title-main">HNRNPA2B1</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the HNRNPA2B1 gene.

<span class="mw-page-title-main">HNRPU</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein U is a protein that in humans is encoded by the HNRNPU gene.

<span class="mw-page-title-main">HNRPD</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) also known as AU-rich element RNA-binding protein 1 (AUF1) is a protein that in humans is encoded by the HNRNPD gene. Alternative splicing of this gene results in four transcript variants.

<span class="mw-page-title-main">HNRNPC</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.

<span class="mw-page-title-main">HNRPUL1</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein U-like protein 1 is a protein that in humans is encoded by the HNRNPUL1 gene.

<span class="mw-page-title-main">HNRNPL</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein L is a protein that in humans is encoded by the HNRNPL gene.

<span class="mw-page-title-main">HNRNPAB</span> Protein-coding gene in humans

Heterogeneous nuclear ribonucleoprotein A/B, also known as HNRNPAB, is a protein which in humans is encoded by the HNRNPAB gene. Although this gene is named HNRNPAB in reference to its first cloning as an RNA binding protein with similarity to HNRNP A and HNRNP B, it is not a member of the HNRNP A/B subfamily of HNRNPs, but groups together closely with HNRNPD/AUF1 and HNRNPDL.

<span class="mw-page-title-main">A1CF</span> Protein-coding gene in the species Homo sapiens

APOBEC1 complementation factor is a protein that in humans is encoded by the A1CF gene.

<span class="mw-page-title-main">HNRNPR</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the HNRNPR gene.

<span class="mw-page-title-main">SYT2</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-2 is a protein that in humans is encoded by the SYT2 gene.

<span class="mw-page-title-main">SYT9</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-9 is a protein that in humans is encoded by the SYT9 gene.

<span class="mw-page-title-main">HNRPDL</span> Mammalian protein found in Homo sapiens

Heterogeneous nuclear ribonucleoprotein D-like, also known as HNRPDL, is a protein which in humans is encoded by the HNRPDL gene.

<span class="mw-page-title-main">SYT7</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-7 is a protein that in humans is encoded by the SYT7 gene.

<span class="mw-page-title-main">PTBP1</span> Protein-coding gene in the species Homo sapiens

Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000135316 – Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 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. 1 2 3 4 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. 1 2 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. 1 2 3 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. 1 2 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. 1 2 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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