Ask about this productRelated genes to: LARP1 antibody
- Gene:
- LARP1 NIH gene
- Name:
- La ribonucleoprotein domain family member 1
- Previous symbol:
- -
- Synonyms:
- LARP, KIAA0731, MGC19556
- Chromosome:
- 5q33.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-16
- Date modifiied:
- 2015-11-18
Related products to: LARP1 antibody
Related articles to: LARP1 antibody
- The synthesis of ribosomes in metazoans is an essential process that is dysregulated in disease. Previous studies implicate La-related protein 1 (LARP1) in binding inactive ribosomes and in repressing Terminal OligoPyrimidine motif mRNAs (TOPs), which encode ribosomal proteins. While the molecular details of LARP1 binding to the ribosome and to TOP mRNAs are deciphered, the mechanistic link between these two activities is not understood. Here, we show that ribosome binding is an essential step in LARP1-mediated TOP repression. LARP1's ribosome binding region is part of a previously unrecognized RNA recognition motif (RRM) domain, which in turn directly interacts with its TOP-binding HEAT repeat domain. Remarkably, ribosome binding is both sufficient and required in cells for LARP1 to bind, repress, and stabilize TOPs via unfolding and remodeling of the RRM domain. Disrupting the coordinated architecture of these domains by mutating the RRM constitutively represses TOPs and compromises cell fitness. Together, these data reveal a general ribosome-sensing function of LARP1, orchestrated through the unique coordinating role of its RRM, which tunes the synthesis of ribosomal proteins to cellular demand for ribosomes. - Source: PubMed
Publication date: 2026/04/19
Saba James AWhite Phoebe EBurroughs A MaxwellAravind LGreen Rachel - Mammalian spermatogenesis is a complex process involving precisely regulated transcription and translation. The RNA-binding protein La ribonucleoprotein domain family member 1 (LARP1) is a member of the LARP family whose role in mammalian spermatogenesis is unclear. This study demonstrates that Larp1 is essential for normal spermatogenesis in mice. Deficiency of Larp1 in male germ cells disrupted meiotic progression and triggered apoptosis, leading to germ cell depletion. Furthermore, it caused aberrant spermatid flagella assembly alongside defects in sperm head morphology and acrosome structure. These cellular abnormalities culminated in impaired sperm motility and a significant reduction in male fertility. Transcriptomic analysis revealed that Larp1 loss upregulates pro-apoptotic genes and hyperactivates the p38 MAPK/p53 pathways, concomitant with the downregulation of genes essential for spermatogenesis, flagellar assembly, acrosome formation, and sperm motility. This altered expression profile thereby provides a mechanistic basis for the observed phenotypic defects. In contrast, female mutant mice exhibited normal oocyte development and fertility. In summary, this study establishes LARP1 as essential for spermatogenesis and male fertility in mice. - Source: PubMed
Fan XuYang LingLi HongWang Zhengpin - Cytoplasmic poly(A)-binding protein (PABPC1) binds the mRNA poly(A) tail via its RNA recognition motifs (RRMs) and recruits factors involved in mRNA metabolism through its C-terminal MLLE domain. The MLLE domain recognizes short PAM2 motifs found in a wide range of regulatory proteins known as PAM2-containing proteins (PACs). Members of the La-related protein (LARP) family, specifically LARP1 and LARP4, which are involved in poly(A) tail protection, contain atypical PAM2 sequences that diverge from the canonical consensus yet retain MLLE binding. The molecular basis of this interaction is not fully understood for LARP1. Here, we combined nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry (ITC), and AlphaFold3 modeling to characterize the interaction between the LARP1 PAM2 motif and the MLLE domain of PABPC1. NMR chemical shift perturbations and heteronuclear NOE analyses defined the MLLE-binding segment, i.e. PAM2 motif, within LARP1. Mutagenesis studies and ITC confirmed the essential role of phenylalanine 496 for MLLE binding. AlphaFold3 modeling corroborated these findings with the prediction of a single turn α-helix in the PAM2 motif. Together, these results define a non-canonical PAM2-MLLE interaction and reveal unexpected plasticity in the recognition of PAM2 motifs by the MLLE domain. - Source: PubMed
Publication date: 2026/02/26
Behvarmanesh AliKozlov GuennadiSprules TaraGehring Kalle - The utility of messenger RNA (mRNA) as a therapeutic modality has been widely demonstrated with the containment of COVID-19, yet the decisions in sequence design in the untranslated regions (UTRs) remain largely unexplored, especially in preclinical models. Here, we focus on the 5' UTR of mRNA and discover sequences that improve therapeutic potential in mouse models of aging and obesity. Bioinformatic analysis of RNA sequencing (RNA-seq), single-cell RNA-seq, ribosome profiling, and crosslinking and immunoprecipitation followed by sequencing data revealed that ribosomal protein (RP) mRNAs are abundant and ubiquitous but undergo distinct translational regulation by LARP1 and LARP4. Of 11 RP mRNAs, we find that the 5' UTRs of RPL18, RPL35, and RPS9 improve the protein output of synthetic mRNAs in human and mouse cells. Investigation of mutant 5' UTRs indicates that this improvement is independent of its terminal oligopyrimidine motif but strong in cells with high levels of reactive oxygen species. In aged mice and mice receiving a high-fat diet, synthetic mRNAs with the 5' UTR of RPS9 resulted in improved protein expression and enhanced humoral immunity through T helper cell 2 cytokines when encoding viral antigens. Altogether, our results highlight the importance of UTR sequence in expanding the therapeutic potential of synthetic mRNAs for aged individuals and those diagnosed with obesity. - Source: PubMed
Publication date: 2026/01/02
Yoon SubinCho HyeonggonLee JisunHa SunghyunLee SuyeonLee Yu-SunCho YoungranHa DahyeonOh AyoungLee SeonghyunJeong DaheeCho JunPark Sang-InNam Jae-HwanLee Young-Suk - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape strategies include general inhibition of host gene expression referred to as host shutoff. Viral nonstructural protein 1 (Nsp1) is the main host shutoff factor that blocks protein translation and induces messenger RNA (mRNA) cleavage and degradation. Viral mRNAs are resistant to the translation shutoff and cleavage induced by Nsp1, and the 5' leader sequence present in all viral mRNAs has been shown to confer resistance. However, the exact molecular mechanism for escape from Nsp1 host shutoff has not been demonstrated. In our previous work, we analyzed the effects of Nsp1 on the expression and function of cellular proteins important for stress granule formation. We discovered that the host transcript for the TIA1 cytotoxic granule-associated RNA-binding protein-like 1 (TIAL1, commonly referred to as TIAR) is resistant to SARS-CoV-2 Nsp1 host shutoff. In this work, using reporter shutoff assays, we examined sequence and structural features of the TIAR 5' untranslated region (UTR) and discovered that the first 23 nt of the TIAR transcript are both necessary and sufficient to confer resistance to the Nsp1. Furthermore, our work revealed that the lack of guanosines within a window of 10-18 nt downstream from the 5' end is a defining feature of Nsp1-resistant transcripts shared between the SARS-CoV-2 leader sequence and the TIAR 5' UTR. Our findings are consistent with the model in which sequence features of 5' UTRs, rather than their secondary structure, confer resistance to Nsp1 host shutoff to both viral and cellular mRNAs. - Source: PubMed
Publication date: 2026/02/17
Galbraith CalebStolz MadeleineTersteeg ScottAndrews EmilyPatel Trushar RKhaperskyy Denys A