EST1A antibody
- Known as:
- EST1A (anti-)
- Catalog number:
- orb101506
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Biorbyt biorb
- Gene target:
- EST1A antibody
Related genes to: EST1A antibody
- Gene:
- SMG6 NIH gene
- Name:
- SMG6 nonsense mediated mRNA decay factor
- Previous symbol:
- C17orf31
- Synonyms:
- KIAA0732, SMG-6, EST1A
- Chromosome:
- 17p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-12-19
- Date modifiied:
- 2019-01-25
Related products to: EST1A antibody
Related articles to: EST1A antibody
- Endogenous circular RNAs (circRNAs) are predominantly generated by a back-splicing process. Due to their lacking 5' and 3' termini, circRNA degradation is exclusively dependent on endoribonucleolytic cleavage. In addition, translation occurring on circRNAs depends solely on internal ribosome entry site (IRES) or IRES-like features, such as an exon junction complex (EJC) deposited after back-splicing. However, the potential relationship between the translatability and stability of circRNAs has yet to be explored. Here, we demonstrate that translatable circRNAs can be subject to canonical EJC-dependent nonsense-mediated mRNA decay (NMD), a well-known mRNA surveillance mechanism, as long as circRNAs contain EJC(s) downstream of a translation termination codon. We find that the NMD of translatable circRNAs involves UPF1 and the NMD-specific endoribonuclease SMG6. This distinct pathway is termed NMD-like circRNA decay (NCD). The differences in factor requirements between canonical EJC-dependent NMD and NCD lead to variations in RNA regulation under cellular stress conditions. Our observations provide an additional layer in the molecular regulation of circRNA dynamics. - Source: PubMed
Publication date: 2026/04/26
Kang EunchaeKang DahyeonCho Yeo KyungShin Min-KyungBoo Sung HoChang JeeyoonKim Hyeong-InJo Jae HeeKim Yoon Ki - Nonsense-mediated mRNA decay (NMD) is one of the most extensively studied pathways of cytoplasmic mRNA degradation. It plays a critical role in diverse cellular processes by eliminating aberrant transcripts containing premature stop codons and by regulating the stability of physiological mRNAs. NMD factors were initially identified through genetic screens in S. cerevisiae (UPF1, 2, 3) and C. elegans (SMG-1, SMG5-7). Subsequent biochemical and genetic studies revealed the composition of NMD complexes and identified additional factors. A major protein hub for NMD is Upf1, an ATP-dependent RNA helicase that is part of two mutually exclusive NMD assemblies, the Upf1-Upf2-Upf3 complex and the Upf1-decapping complex, which contains the decapping enzyme and its co-factors. Here, we discuss recent findings, primarily from budding yeast, on the protein-protein interactions driving NMD complexes dynamics and their similarities to human NMD. Together, the N-terminal cysteine and histidine rich (CH) and helicase domains (HD) of Upf1 act as a hub for binding multiple partners. Upf1 is required for binding to NMD substrates and for the initiation of RNA degradation through decapping (yeast) or endonucleolytic hydrolysis (humans). We focus on the interplay between Upf2, Dcp2 and Nmd4 (yeast SMG6), which ensures the mutually exclusive formation of Upf1-bound subcomplexes modulating Upf1's affinity for RNA. Thus, the study of NMD factors interactions in different organisms sheds new light on the remarkable conservation of NMD molecular mechanisms. - Source: PubMed
Publication date: 2026/03/10
Ruiz-Gutierrez NadiaGraille MarcLe Hir HervéSaveanu Cosmin - Three new studies (Arpa et al., 169734 [2026]; Kurscheidt et al., 17: 1934 [2026]; Modena et al., , this issue [2026]) found that the PIN domains of SMG5 and SMG6, two proteins involved in nonsense-mediated mRNA decay (NMD), interact and show that the physiological endonucleolytic activity initiating the degradation of the nonsense mRNA is exerted by this composite catalytic site. - Source: PubMed
Publication date: 2026/05/18
Mühlemann OliverKarousis Evangelos D - Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase. - Source: PubMed
Publication date: 2026/02/26
Arpa Enes STaschner MichaelDe Matos MaraJonas StefanieGatfield David - Nonsense-mediated mRNA decay (NMD) relies on the coordinated assembly and action of multiple protein factors. Degradation of target mRNAs begins with endonucleolytic cleavage near premature stop codons, but the mechanisms of endonuclease activation and regulation remain unclear. Using structural predictions, biochemical in vitro assays, and cell-based NMD analysis, we show that SMG5 and SMG6 interact via their PIN domains to form a composite interface (cPIN) with full endonuclease activity. In vitro reconstituted SMG5-SMG6 cPIN heterodimers show high activity, as SMG5 completes the SMG6 active site and substrate binding site. Mutations in residues at their predicted interaction surfaces, RNA-binding sites, or active site attenuate or abolish cPIN activity in vitro and impair cellular NMD. Our findings demonstrate how paralogous PIN domains complement each other to assemble a highly active endonuclease in NMD, providing a structural and mechanistic explanation for efficient NMD substrate degradation. - Source: PubMed
Publication date: 2026/02/19
Kurscheidt KatharinaTheunissen SophiePasquali NataliaBecker KerstinBoehm VolkerConti ElenaGehring Niels H