Ask about this productRelated genes to: LAS1L antibody
- Gene:
- LAS1L NIH gene
- Name:
- LAS1 like, ribosome biogenesis factor
- Previous symbol:
- -
- Synonyms:
- FLJ12525
- Chromosome:
- Xq12
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-26
- Date modifiied:
- 2016-06-13
Related products to: LAS1L antibody
Related articles to: LAS1L antibody
- Rixosome is a conserved, multi-subunit protein complex that has critical roles in ribosome biogenesis and silencing of Polycomb target genes. The subunits of human rixosome include PELP1, WDR18, TEX10, LAS1L and NOL9, with LAS1L providing the endoribonuclease activity and NOL9 the RNA 5' kinase activity. We report here cryo-EM structures of the human PELP1-WDR18-TEX10 and LAS1L-NOL9 complexes and a lower-resolution model of the human PELP1-WDR18-LAS1L complex. The structures reveal the overall organization of the human rixosome core scaffold of PELP1-WDR18-TEX10-LAS1L and indicate how the LAS1L-NOL9 endonuclease/kinase catalytic module is recruited to this core scaffold. Each TEX10 molecule has two regions of contact with WDR18, while the helix at the C terminus of WDR18 interacts with the helical domain of LAS1L. The structural observations are supported by our mutagenesis studies. Mutations in both WDR18-TEX10 contact regions can block the binding of TEX10, while truncation of the C-terminal helix of WDR18 can abolish the binding of LAS1L. The structures also reveal substantial conformational differences for TEX10 between the PELP1-WDR18-TEX10 complex alone and that in complex with pre-ribosome. - Source: PubMed
Publication date: 2025/04/07
Huang JiTong Liang - Ribosome biogenesis is a highly regulated cellular process requiring a large cohort of accessory factors to ensure the accurate production of ribosomes. Dysregulation of ribosome biogenesis is associated with the development of various human diseases, including cancer. The Las1L-Nol9 endonuclease-kinase complex is essential for the cleavage of the rRNA internal transcribed spacer 2 (ITS2), the phosphorylation of the 5'-hydroxyl end of the resulting precursor, and, thus, the maturation of the 60S ribosome. However, how the Las1L-Nol9 complex is regulated in cells is unclear. In this study, we report that the nucleolar ubiquitin-specific protease USP36 is a novel regulator of the Las1L-Nol9 complex. USP36 interacts with both Las1L and Nol9 and regulates their stability via deubiquitination. Intriguingly, USP36 also mediates the SUMOylation of Las1L, mainly at lysine (K) 565. Mutating K565 to arginine (R) does not affect the levels of Las1L and the formation of the Las1L-Nol9 complex, but abolishes its function in ITS2 processing, as unlike wild-type Las1L, the K565R mutant failed to rescue the defects in the ITS2 processing induced by the knockdown of endogenous Las1L. These results suggest that USP36-mediated Las1L SUMOylation is critical for ITS2 processing and that USP36 plays a critical role in ribosome biogenesis by regulating the Las1L-Nol9 complex. - Source: PubMed
Li YanpingYang YunhanSears Rosalie CDai Mu-ShuiSun Xiao-Xin - Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Oncogenic PELP1 is frequently overexpressed in TNBC, and it has been demonstrated that PELP1 signaling is essential for TNBC progression. The therapeutic utility of targeting PELP1 in TNBC, however, remains unknown. In this study, we investigated the effectiveness of SMIP34, a recently developed PELP1 inhibitor for the treatment of TNBC. - Source: PubMed
Publication date: 2023/05/18
Altwegg Kristin APratap Uday PLiu ZexuanLiu JunhaoSanchez John RYang XueEbrahimi BehnamPanneerdoss Durga MeenakshiLi XiaonanSareddy Gangadhara RViswanadhapalli SuryavathiRao Manjeet KVadlamudi Ratna K - Tumor metastasis is still an insurmountable obstacle in tumor treatment. Lung cancer represents one of the most common malignancies with high morbidity worldwide. hnRNPA1 has been reported to be involved in the regulation of tumor metastasis, while its specific role in tumor metastasis seems to be controversial and its molecular mechanism in lung cancer metastasis remains to be further elucidated. In this study, we confirmed that knockdown of the hnRNPA1 led to enhanced migration, invasion and EMT transition in lung cancer cells. Bioinformatics analysis of the GSE34992 dataset revealed that hnRNPA1 may regulate the alternative splicing (AS) of LAS1L exon 9. Further AGE assays and RIP assays revealed that hnRNPA1 can directly bind to the LAS1L pre-mRNA to inhibit the splicing of LAS1L exon 9. The RNA pull-down assays showed that hnRNPA1 can specifically bind to the two sites (UAGGGU(WT1) and UGGGGU(WT3)) of LAS1L Intron 9. Further Transwell assays indicated that the expression ratio of LAS1L-L/LAS1L-S regulated by hnRNPA1 can further promote the migration, invasion and EMT transition in lung cancer cells. Moreover, hnRNPA1 expression showed significant heterogeneity in lung cancer tissues, which may contain new research directions and potential therapeutic targets. Our results indicate that hnRNPA1 can affect the metastasis of lung cancer cells by modulating the AS of LAS1L exon 9, highlighting the potential significance of hnRNPA1 in lung cancer metastasis. - Source: PubMed
Publication date: 2022/06/23
Han PengCao PengYue JiaqiKong KangleHu ShanDeng YuLi LequnLi FanZhao Bo - LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson−Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we present an eighteen-month old boy with a phenotype of spinal muscular atrophy with respiratory distress (SMARD). By applying WES, we identified a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G > C, p.Thr282=). We suggest that the identified variant impairs the RNA splicing process. Furthermore, we proved the absence of any coding regions by qPCR and sequencing cDNA using amplicon deep sequencing and Sanger sequencing methods. According to the SMARD phenotype, severe breathing problems causing respiratory insufficiency, hypotonia, and feeding difficulties were observed in our patient from the first days of life. Remarkably, our case is the second described patient with a SMARD-like phenotype due to a mutation in the LAS1L gene and the first with a variant impacting splicing. - Source: PubMed
Publication date: 2022/04/21
Stembalska AgnieszkaRydzanicz MałgorzataWalas WojciechGasperowicz PiotrPollak AgnieszkaPienkowski Victor MurciaBiela MateuszKlaniewska MagdalenaGamrot ZuzannaGronska EwaPloski RafalSmigiel Robert