Ask about this productRelated genes to: SMNDC1 Blocking Peptide
- Gene:
- SMNDC1 NIH gene
- Name:
- survival motor neuron domain containing 1
- Previous symbol:
- -
- Synonyms:
- SPF30, SMNR, TDRD16C
- Chromosome:
- 10q25.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-06
- Date modifiied:
- 2016-10-05
Related products to: SMNDC1 Blocking Peptide
Related articles to: SMNDC1 Blocking Peptide
- Alternative splicing is a key post-transcriptional process that generates multiple mRNAs from a single pre-mRNA through the coordinated action of the spliceosome and associated splicing factors. SMNDC1 (survival motor neuron domain containing 1) has been identified as an integral component of the spliceosome complex. Previous studies have shown that SMNDC1 is essential for splicing catalysis in vitro and plays a regulatory role in intron retention in cancer. However, the phylogenetic relationships and expression patterns of SMNDC1 across the animal kingdom have not been systematically investigated. In this study, we conducted a comprehensive phylogenetic analysis of SMNDC1 genes in animals. A total of 72 SMNDC1 genes were identified from 66 animal species. Bioinformatic analyses revealed that the gene structure and protein domains of SMNDC1 are highly conserved, with only a few species possessing gene duplications. Notably, the human SMNDC1 gene exhibits elevated expression levels in multiple cancer types, including breast, colon, and rectal cancers, suggesting its potential role in tumor development and its value as a diagnostic or therapeutic target. Overall, our findings provide a systematic overview of the SMNDC1 gene family in animals and establish a foundation for future studies exploring its molecular functions and evolutionary significance. - Source: PubMed
Zhang Jing-WanWang Hong-MeiOuyang GuojunSun ChaoHuang Bao-Xing - Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy that lacks reliable biomarkers to guide treatment decisions. Effective prognostic tools are needed to improve its clinical management. We conducted a comprehensive proteomic analysis on 115 PDA patient samples with matched adjacent normal tissue. A 20-protein diagnostic panel was identified (LGALS1, ANXA2, LGALS3BP, CTSD, S100P, COL12A1, SFN, THBS2, CTHRC1, THBS1, SERPINB5, LAMC2, POSTN, CEACAM6, CTSE, PLEC, PKM, S100A11, TAGLN2, ALDOA). Consensus clustering analysis identified four prognostic proteomic subtypes. Subtypes with poorer prognoses exhibited upregulation of neutrophil degranulation, extracellular matrix remodeling, focal adhesion, Mesenchymal Epithelial Transition, collagen formation, and PI3K-Akt-mTOR-related pathways, indicating a predominance of basal-like and activated stromal features. In tumors with homologous recombination deficiency or Catalogue of Somatic Mutations in Cancer Signature-3, several immune-related proteins were enriched. An 18-protein (PURB, SDCBP2, CD2BP2, GALM, SERPINA3, OAS3, FAN1, ZPR1, KRT2, NUDT2, SMNDC1, SERPINA4, CUTA, WDR36, POSTN, CLEC11A, PEX14, and PI4KA) risk score was developed and validated using multicox regression analyses with LASSO regularization. The risk score demonstrated independent prognostic significance for overall survival and recurrence, and was validated in an independent proteomic dataset generated using a different proteomic technology. This study thus introduces four novel prognostic PDA subtypes, and an 18-protein risk score validated in an independent dataset, which shows promise for improving survival prediction and could serve as a valuable tool for personalized treatment guidance. - Source: PubMed
Aref Adel TGrealey JasonPathan MohashinNoor ZainabAnees AsimAzad A K MSmith Daniela LeeHumphries Erin MBucio-Noble DanielKoh Jennifer M SSykes Erin KWilliams Steven GLyons Ruth JLucas NatashaXavier DylanSahni SumitMittal AnubhavSamra Jaswinder SPearson John VWaddell NicolaKondrashova OlgaChou AngelaSioson LorettaSheen Amy Hains Peter GRobinson Phillip JZhong QingReddel Roger RGill Anthony J - Motor neuron-related splicing factor 30 (SPF30, also known as SMNDC1) is a paralog of the survival motor neuron protein that regulates the expression of various genes by affecting mRNA splicing. SPF30 has an autoregulatory mechanism that controls its expression. However, the detailed molecular mechanisms determining cellular levels of SPF30 remain unclear. Here, we demonstrated that SPF30 expression was controlled via the negative autoregulatory feedback, whereby increased SPF30 expression caused the inclusion of cassette exon within intron 2 and/or the generation of a newly spliced variant with exon 4a (produced by splicing 17 bases upstream of the canonical intron 3 and exon 4 junction). Altered transcripts with cassette exon or exon 4a were subjected to nonsense-mediated mRNA decay, leading to reduced SPF30 mRNA levels. Conversely, the loss of SPF30 protein resulted in a drastic reduction in the alternative exon 4a splice site usage compared to cassette exon inclusion, suggesting that alternative splicing at exon 4a contributes more to adjusting SPF30 expression levels. An in vivo splicing assay designed to reflect the usage of alternative exon 4a splice site demonstrated that a short stretch of sequence within exon 4 of SPF30 mRNA was required for the alternative splicing at exon 4a. In addition, the C terminal region of SPF30, particularly the latter part of α-helix and a kink-like structure, was crucial for the autoregulatory mechanism by enabling binding to exon 4a-containing RNA. These results reveal the molecular basis of the autoregulatory mechanism underlying SPF30 gene expression. - Source: PubMed
Publication date: 2025/07/25
Izumikawa KeiichiShida TatsuyaOnodera YuukaTashima YuitoMiyao SotaroSuda TomomiSuda YasuyukiKamimura RyosukeNagai MaikoSugihara MinoruNoguchi TamotsuNagahama Masami - A previous study using Thermostable Group II Intron Reverse Transcriptase sequencing (TGIRT-seq) found human plasma contains short (≤300 nt) structured full-length excised linear intron (FLEXI) RNAs with potential to serve as blood-based biomarkers. Here, TGIRT-seq identified >9,000 different FLEXI RNAs in human cell lines, including relatively abundant FLEXIs with cell-type-specific expression patterns. Analysis of public CLIP-seq datasets identified 126 RNA-binding proteins (RBPs) that have binding sites within the region corresponding to the FLEXI or overlapping FLEXI splice sites in pre-mRNAs, including 53 RBPs with binding sites for ≥30 different FLEXIs. These included splicing factors, transcription factors, a chromatin remodeling protein, cellular growth regulators, and proteins with cytoplasmic functions. Analysis of ENCODE datasets identified subsets of these RBPs whose knockdown impacted FLEXI host gene mRNA levels or proximate alternative splicing, indicating functional interactions. Hierarchical clustering identified six subsets of RBPs whose FLEXI binding sites were co-enriched in six subsets of functionally related host genes: AGO1-4 and DICER, including but not limited to agotrons or mirtron pre-miRNAs; DKC1, NOLC1, SMNDC1, and AATF (Apoptosis Antagonizing Transcription Factor), including but not limited to snoRNA-encoding FLEXIs; two subsets of alternative splicing factors; and two subsets that included RBPs with cytoplasmic functions (e.g., LARP4, PABPC4, METAP2, and ZNF622) together with regulatory proteins. Cell fractionation experiments showed cytoplasmic enrichment of FLEXI RNAs with binding sites for RBPs with cytoplasmic functions. The subsets of host genes encoding FLEXIs with binding sites for different subsets of RBPs were co-enriched with non-FLEXI other short and long introns with binding sites for the same RBPs, suggesting overarching mechanisms for coordinately regulating expression of functionally related genes. Our findings identify FLEXIs as a previously unrecognized large class of cellular RNAs and provide a comprehensive roadmap for further analyzing their biological functions and the relationship of their RBPs to cellular regulatory mechanisms. - Source: PubMed
Publication date: 2024/09/26
Yao JunXu HengyiFerrick-Kiddie Elizabeth ANottingham Ryan MWu Douglas CAres ManuelLambowitz Alan M - Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and organismal size restriction. Together, these models demonstrate the importance of poison exons for both molecular and organismal phenotypes that likely explain their extraordinary conservation. - Source: PubMed
Publication date: 2024/08/16
Belleville Andrea EThomas James DTonnies JacksonGabel Austin MBorrero Rossi AndreaSingh PritiQueitsch ChristineBradley Robert K