Ask about this productRelated genes to: RSRC2 Blocking Peptide
- Gene:
- RSRC2 NIH gene
- Name:
- arginine and serine rich coiled-coil 2
- Previous symbol:
- -
- Synonyms:
- FLJ11021
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2007-02-13
- Date modifiied:
- 2016-06-06
Related products to: RSRC2 Blocking Peptide
Related articles to: RSRC2 Blocking Peptide
- Mitotic fidelity requires proper chromosome alignment at the spindle equator, a process known as chromosome congression, mediated by well-established protein networks. Although RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs) have been implicated in cell division, their functional interplay remains unclear. Here, we show that RSRC2, a poorly characterized RBP, is essential for proper cell division through its interaction with the long ncRNA C1QTNF1-AS1. Loss of either RSRC2 or C1QTNF1-AS1 causes mitotic defects. RSRC2 associates with distinct protein sets involved in splicing and centrosome biogenesis, regulating mitotic gene splicing and maintaining centriole integrity. RSRC2 depletion impairs recruitment of the centrosomal scaffold proteins PCNT and CDK5RAP2, which are essential for organizing microtubules to form the mitotic spindle. While C1QTNF1-AS1 loss does not alter RSRC2 expression or its global interactome, it reduces RSRC2 localization at the centrosome. We also find that C1QTNF1-AS1 directs RSRC2 to the centrosome, where RSRC2, in turn, promotes the recruitment of PCNT mRNA to the centrosome. Our study highlights the critical role of RNA-protein complexes in ensuring error-free mitosis and identifies RSRC2 as a multifunctional protein with dual roles in splicing and centrosome-associated RNA localization. - Source: PubMed
Babaei ParniaCoomer Alice OGeorgieva KaliyaGuiducci GiuliaVitiello ElisaDodel MartinManiati EleniEid Hanya ElsayedThind AnishaKrishnamurthy SnehaNawrocka AnnaWallis SamWang JunShkumatava AlenaMardakheh Faraz KStojic Lovorka - Triple-negative breast cancer (TNBC) has a shorter survival time and higher mortality rate than other molecular subtypes. RSRC2 is a newly discovered tumor suppressor gene. However, the potential functional mechanism of RSRC2 in TNBC remains unknown so far. Multiple bioinformatics databases were used. A Human Transcriptome Array 2.0 analysis, ChIP-seq analysis, ChIP-qPCR, RT-qPCR, Western blot, cell function assays in vitro and a metastatic mouse model in vivo were performed to demonstrate the role of RSRC2 in TNBC. Through the analysis of various databases, RSRC2 expression was the lowest in TNBC tissues compared to other molecular subtypes. The low expression of RSRC2 was associated with a worse prognosis for patients with breast cancer. The transcriptome array, ChIP-seq and bioinformatics analysis identified that GRHL2 and SCIN might have a close relationship with RSRC2. The functional bioinformatics enrichment analysis and functional cell experiments showed that RSRC2 was involved in cell adhesion, cell proliferation, cell migration and invasion. Furthermore, RSRC2 expression suppressed SCIN expression but not GRHL2 expression. SCIN re-expression in the RSRC2 overexpression cells or SCIN knockdown in the RSRC2 knockdown cells reversed the cellular function caused by RSRC2. Mechanistically, RSRC2 transcriptionally inhibited SCIN expression. In summary, our study reveals that RSRC2 acts as a tumor suppressor in TNBC development and progression through negatively regulating SCIN-mediated cell function, thus providing a potential target for TNBC treatment. - Source: PubMed
Publication date: 2023/12/19
Zhao NanNi ChunshengFan ShuaiChe NaLi YanleiWang SongLi YongliDong XueyiGuo YuhongZhao XiulanLiu Tieju - E4B belongs to the U-box E3 ligase family and functions as either an E3 or an E4 enzyme in protein ubiquitination. Transformer2A (TRA2A) and Pyrroline-5-carboxylate reductase 2 (PYCR2) are related to cancer development and are overexpressed in many cancer cells. The degradation of TRA2A and PYCR2 mediated by the ubiquitin-proteasome system (UPS) has not been reported. This study validated that E4B could ubiquitinate TRA2A and PYCR2 as an E3 ligase both and in the HEK293 cells. E4B mediated the degradation by forming K11- and K48- linked polyubiquitin chains on TRA2A and PYCR2, respectively. E4B regulated the alternative splicing function of TRA2A and affected RSRC2 transcription in the HEK293 cells. Although E4B is highly expressed, it hardly degrades TRA2A and PYCR2 in hepatocellular carcinoma (HCC) cells, suggesting other mechanisms exist for degradation of TRA2A and PYCR2 in the HCC cells. We finally reported that E4B interacted with substrates its variable region. - Source: PubMed
Publication date: 2022/05/20
Lu YaoJiang BoPeng KangliLi ShashaLiu XiangnanWang BufanChen YuntianWang TiepengZhao Bo - Genome-wide association studies (GWAS) have identified many disease-associated noncoding variants, but cannot distinguish functional single-nucleotide polymorphisms (fSNPs) from others that reside incidentally within risk loci. To address this challenge, we developed an unbiased high-throughput screen that employs type IIS enzymatic restriction to identify fSNPs that allelically modulate the binding of regulatory proteins. We coupled this approach, termed SNP-seq, with flanking restriction enhanced pulldown (FREP) to identify regulation of CD40 by three disease-associated fSNPs via four regulatory proteins, RBPJ, RSRC2 and FUBP-1/TRAP150. Applying this approach across 27 loci associated with juvenile idiopathic arthritis, we identified 148 candidate fSNPs, including two that regulate STAT4 via the regulatory proteins SATB2 and H1.2. Together, these findings establish the utility of tandem SNP-seq/FREP to bridge the gap between GWAS and disease mechanism. - Source: PubMed
Publication date: 2018/07/16
Li GangMartínez-Bonet MartaWu DiYang YuCui JingNguyen Hung NCunin PierreLevescot AnaïsBai MingWestra Harm-JanOkada YukinoriBrenner Michael BRaychaudhuri SoumyaHendrickson Eric AMaas Richard LNigrovic Peter A - Human GWAS of obesity have been successful in identifying loci associated with adiposity, but for the most part, these are non-coding SNPs whose function, or even whose gene of action, is unknown. To help identify the genes on which these human BMI loci may be operating, we conducted a high throughput screen in Drosophila melanogaster. Starting with 78 BMI loci from two recently published GWAS meta-analyses, we identified fly orthologs of all nearby genes (± 250KB). We crossed RNAi knockdown lines of each gene with flies containing tissue-specific drivers to knock down (KD) the expression of the genes only in the brain and the fat body. We then raised the flies on a control diet and compared the amount of fat/triglyceride in the tissue-specific KD group compared to the driver-only control flies. 16 of the 78 BMI GWAS loci could not be screened with this approach, as no gene in the 500-kb region had a fly ortholog. Of the remaining 62 GWAS loci testable in the fly, we found a significant fat phenotype in the KD flies for at least one gene for 26 loci (42%) even after correcting for multiple comparisons. By contrast, the rate of significant fat phenotypes in RNAi KD found in a recent genome-wide Drosophila screen (Pospisilik et al. (2010) is ~5%. More interestingly, for 10 of the 26 positive regions, we found that the nearest gene was not the one that showed a significant phenotype in the fly. Specifically, our screen suggests that for the 10 human BMI SNPs rs11057405, rs205262, rs9925964, rs9914578, rs2287019, rs11688816, rs13107325, rs7164727, rs17724992, and rs299412, the functional genes may NOT be the nearest ones (CLIP1, C6orf106, KAT8, SMG6, QPCTL, EHBP1, SLC39A8, ADPGK /ADPGK-AS1, PGPEP1, KCTD15, respectively), but instead, the specific nearby cis genes are the functional target (namely: ZCCHC8, VPS33A, RSRC2; SPDEF, NUDT3; PAGR1; SETD1, VKORC1; SGSM2, SRR; VASP, SIX5; OTX1; BANK1; ARIH1; ELL; CHST8, respectively). The study also suggests further functional experiments to elucidate mechanism of action for genes evolutionarily conserved for fat storage. - Source: PubMed
Publication date: 2018/04/02
Baranski Thomas JKraja Aldi TFink Jill LFeitosa MaryLenzini Petra ABorecki Ingrid BLiu Ching-TiCupples L AdrienneNorth Kari EProvince Michael A