Ask about this productRelated genes to: LARP6 antibody
- Gene:
- LARP6 NIH gene
- Name:
- La ribonucleoprotein domain family member 6
- Previous symbol:
- -
- Synonyms:
- acheron, FLJ11196
- Chromosome:
- 15q23
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-16
- Date modifiied:
- 2015-11-18
Related products to: LARP6 antibody
Related articles to: LARP6 antibody
- Metabolic syndrome and excessive alcohol consumption (MetALD) result in liver injury and fibrosis, which are driven by increased collagen production by activated hepatic stellate cells (HSCs). Our previous studies demonstrated that LARP6, an RNA-binding protein, may facilitate collagen production. However, the expression and function of LARP6 as a regulator of fibrosis development in a disease-relevant model remain poorly understood. We demonstrated that LARP6 was upregulated in human activated HSCs in metabolic dysfunction-associated steatohepatitis (MASH) and MetALD. By using single-nucleus RNA-seq and assay for transposase-accessible chromatin sequencing, we showed that JUNB upregulated LARP6 expression in activated HSCs. Moreover, LARP6 knockdown in human HSCs suppressed fibrogenic gene expression. By integrating enhanced crosslinking and IP analysis and ribosome profiling in HSCs, we showed that LARP6 interacted with mature mRNAs comprising more than 300 genes, including RNA structural elements within COL1A1, COL1A2, and COL3A1 to regulate mRNA expression and translation. IP-mass spectrometry analysis demonstrated LARP6 protein-protein interactions with mRNA translation components and the actin cytoskeleton. Furthermore, Dicer substrate siRNA-based HSC-specific gene knockdown or pharmacological inhibition of LARP6 attenuated fibrosis development in human MASH and MetALD liver spheroids. Our results suggest LARP6 plays a key role in fibrogenic gene regulation and that targeting LARP6 in human HSCs may represent a therapeutic approach for liver fibrosis. - Source: PubMed
Publication date: 2026/02/26
Kim Hyun YoungMizrahi OrelLee WonseokRosenthal Sara BHan CuijuanYee Brian ABlue Steven MDiaz JesielJonnalagadda Jyotiprakash PStreet Lena AHokutan KananiJang HaeumMiciano CharleneMa Chen-TingBobkov Andrey ASergienko EduardJackson Michael RJovanovic MarkoStefanovic BrankoKisseleva TatianaYeo Gene WBrenner David A - Intrinsically disordered regions (IDRs) are prevalent in RNA-binding proteins (RBPs), yet their roles in RNA interactions remain poorly defined. We examined RNA-binding regulation by structured and disordered regions of LARP6, an RBP with a diverse RNA-binding repertoire. Mass spectrometry-based RNA interaction mapping in living cells identified direct LARP6-RNA contacts within the structured La-module and its flanking IDRs. Mutagenesis and individual-nucleotide resolution UV-crosslinking and immunoprecipitation (iCLIP) revealed the La-module, but not the IDRs, as essential for LARP6 RNA binding. Deletion of the N-terminal IDR broadened LARP6 RNA footprints, uncovering a role in RNA-binding selectivity. This is achieved through a composite mechanism of restricting the conformational flexibility of the adjacent La-module, forming auxiliary contacts with the RNA, and modulating RNA access for binding. The IDR-mediated RNA-binding selectivity is critical for LARP6-mediated promotion of cancer cell viability and invasion. Our findings uncover a previously unrecognised critical function for IDRs in promoting selective RBP-RNA recognition, by affecting the binding specificity of their adjacent structured domains. - Source: PubMed
Publication date: 2026/02/19
Capraro FedericaAbis GiancarloIncocciati AlessioSimpson Peter JKarimzadeh MehranMasino LauraBarley AlexanderBui Tam T TKelly GeoffGoodarzi HaniConte Maria RMardakheh Faraz K - - Source: PubMed
Publication date: 2025/09/15
Bettadapura Sharanya SSatyanarayana Sushumna BBruns Danielle R - La ribonucleoprotein 6, translational regulator (LARP6), a multifunctional mRNA-binding protein with well-described profibrotic effects, increases type I collagen mRNA half-life, translation, and deposition in noncardiac tissues. In the heart, LARP6 is expressed in cardiomyocytes, not primarily involved in fibrosis, where its role is unknown. To investigate the role of cardiomyocyte-derived LARP6 on cardiac function and remodeling, we generated a cardiomyocyte-specific LARP6 overexpressing transgenic mouse model (LARP6-Tg). Baseline longitudinal studies up to 10 mo of age revealed that constitutive overexpression of LARP6 had no significant effect on cardiac function or morphology despite inducing mild interstitial fibrosis versus wild-type (WT) littermates. Subsequently, we hypothesized that cardiomyocyte-specific LARP6-Tg mice would exhibit exacerbated cardiac remodeling and dysfunction in response to hypertensive stress via angiotensin II (Ang II) infusion. Ang II (1000 ng/kg/min for 21 days) induced hypertension and cardiac hypertrophy in WT and LARP6-Tg mice of both sexes. Unexpectedly, Ang II-induced cardiac dysfunction was prevented in LARP6-Tg mice. Cardiac gene expression profiling predicted increased fibrosis and cardiomyocyte death in Ang II-treated WT mice and inhibition of cardiomyocyte death in Ang II-treated LARP6-Tg mice versus saline-treated controls. Surprisingly, Ang II-induced interstitial fibrosis was reduced in LARP6-Tg mice and associated with attenuation of cardiomyocyte cell death and reduced fibroblast activation. These data support a mild profibrotic action of cardiomyocyte-specific LARP6 overexpression in unstressed mice and, paradoxically, that LARP6 overexpression is sufficient to prevent Ang II-induced cardiac interstitial fibrosis and dysfunction. Sustained induction of LARP6 has therapeutic potential in hypertensive heart disease. LARP6 is a novel multifunctional RNA-binding protein whose role in the heart is poorly understood. Transgenic overexpression of LARP6 in cardiomyocytes caused mild cardiac fibrosis under basal conditions with no impact on cardiac function but, unexpectedly, blunted angiotensin-II-induced cardiac fibrosis and dysfunction. This protective effect of LARP6 overexpression was associated with significant shifts in the cardiac transcriptome alongside blunted fibroblast activation and cardiomyocyte apoptosis under hypertension conditions, highlighting LARP6 as a novel therapeutic target. - Source: PubMed
Publication date: 2025/08/18
Russell Jacob JYoshida TadashiMa LixinLee LiDavis Daniel JGrisanti Laurel ARuff MargotBailey Chastidy ABender Shawn BChandrasekar Bysani - La-related proteins (LARPs) are RNA-binding proteins that are involved in a variety of disease-related processes. Most LARPs recognize short single-stranded poly(U/A) motifs via a conserved hydrophobic pocket. Human LARP6 (HsLARP6) is an exception, binding a structured 5' stem-loop (5'SL) that controls type I collagen translation and fibroproliferative disease progression. Here, we present the de novo solution nuclear magnetic resonance structure of the La domain of HsLARP6 in the bound state. Chemical shift perturbation, solvent paramagnetic relaxation enhancement, intermolecular nuclear Overhauser effects, and targeted mutagenesis converge on a previously unknown binding interface that integrates electrostatic and hydrophobic contacts with shape complementarity in 5'SL binding. This noncanonical interface enables the La domain to discriminate 5'SL RNA from homopolymeric or purely helical hairpin RNAs with low-nanomolar affinity, overturning earlier views that the adjacent RNA recognition motif is required for recognition. The structure provides the first molecular model for 5'SL recognition and expands the paradigm of La-mediated RNA binding beyond 3'-terminal oligo-U/A motifs. These insights provide the biophysical framework for molecular recognition of 5'SL by LARP6 that is related to collagen biosynthesis in fibrosis and associated pathologies. - Source: PubMed
Gordon Blaine HOgunkunle Victoria SSilvers Robert