La-related Protein Research Articles

The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass

Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5′ terminal oligopyrimidine tract (5′TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human β-cells, being 2–4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in β-cells (β-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the β-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and β-cell mass were observed in the β-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in β-cells.

The isolated La-module of LARP1 mediates 3’ poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1

ABSTRACT The protein domain arrangement known as the La-module, comprised of a La motif (LaM) followed by a linker and RNA recognition motif (RRM), is found in seven La-related proteins: LARP1, LARP1B, LARP3 (La protein), LARP4, LARP4B, LARP6, and LARP7 in humans. Several LARPs have been characterized for their distinct activity in a specific aspect of RNA metabolism. The La-modules vary among the LARPs in linker length and RRM subtype. The La-modules of La protein and LARP7 bind and protect nuclear RNAs with UUU-3ʹ tails from degradation by 3ʹ exonucleases. LARP4 is an mRNA poly(A) stabilization factor that binds poly(A) and the cytoplasmic poly(A)-binding protein PABPC1 (also known as PABP). LARP1 exhibits poly(A) length protection and mRNA stabilization similar to LARP4. Here, we show that these LARP1 activities are mediated by its La-module and dependent on a PAM2 motif that binds PABP. The isolated La-module of LARP1 is sufficient for PABP-dependent poly(A) length protection and mRNA stabilization in HEK293 cells. A point mutation in the PAM2 motif in the La-module impairs mRNA stabilization and PABP binding in vivo but does not impair oligo(A) RNA binding by the purified recombinant La-module in vitro. We characterize the unusual PAM2 sequence of LARP1 and show it may differentially affect stable and unstable mRNAs. The unique LARP1 La-module can function as an autonomous factor to confer poly(A) protection and stabilization to heterologous mRNAs.

The SARS-CoV-2 RNA\u2013protein interactome in infected human cells

Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.

Quality-Control Mechanism for Telomerase RNA Folding in the Cell

Long non-coding RNAs can often fold into different conformations. Telomerase RNA, an essential component of the telomerase ribonucleoprotein (RNP) enzyme, must fold into a defined structure to fulfill its function with the protein catalytic subunit (TERT) and other accessory factors. However, the mechanism by which the correct folding of telomerase RNA is warranted in a cell is still unknown. Here we show that La-related protein Pof8 specifically recognizes the conserved pseudoknot region of telomerase RNA and instructs the binding of the Lsm2-8 complex to its mature 3' end, thus selectively protecting the correctly folded RNA from exonucleolytic degradation. In the absence of Pof8, TERT assembles with misfolded RNA and produces little telomerase activity. Therefore, Pof8 plays a key role in telomerase RNA folding quality control, ensuring that TERT only assembles with functional telomerase RNA to form active telomerase. Our finding reveals a mechanism for non-coding RNA folding quality control.

Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.

SummaryTranslation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT.

Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins

ABSTRACT La-related proteins 7 (LARP7) are a class of RNA chaperones that bind the 3′ ends of RNA and are constitutively associated with their specific target RNAs. In metazoa, Larp7 binds to the long non-coding 7SK RNA as a core component of the 7SK RNP, a major regulator of eukaryotic transcription. In the ciliate Tetrahymena the LARP7 protein p65 is a component of telomerase, an essential ribonucleoprotein complex that maintains the telomeric DNA at eukaryotic chromosome ends. p65 is important for the ordered assembly of telomerase RNA (TER) with telomerase reverse transcriptase. Unexpectedly, Schizosaccharomyces pombe Pof8 was recently identified as a LARP7 protein and a core component of fission yeast telomerase essential for biogenesis. LARP7 proteins have a conserved N-terminal La motif and RRM1 (La module) and C-terminal RRM2 with specific RNA substrate recognition attributed to RRM2, first structurally characterized in p65 as an atypical RRM named xRRM. Here we present the X-ray crystal structure and NMR studies of S. pombe Pof8 RRM2. Sequence and structure comparison of Pof8 RRM2 to p65 and human Larp7 xRRMs reveals conserved features for RNA binding with the main variability in the length of the non-canonical helix α3. This study shows that Pof8 has conserved xRRM features, providing insight into TER recognition and the defining characteristics of the xRRM.

Human La Protein: An RNA-Binding Protein Involved in Ovarian Cancer Development and Multidrug Resistance.

Multidrug resistance is the main cause of chemotherapy failure and death in patients with advanced ovarian cancer. Drug resistance is a problem that must be solved to improve the survival rate of patients with advanced ovarian cancer. The RNA-binding protein La and the La-related protein family are highly expressed in various malignant tumors, including ovarian cancer. This article reviews the mechanisms of La protein in tumorigenesis, development, and drug resistance. High La protein expression in tumor cells promotes tumor proliferation, invasion, and migration; disrupts cell cycle; and inhibits tumor cell apoptosis caused by chemotherapeutic drugs through various pathways, resulting in chemotherapy resistance in ovarian cancer. Further study of the role of La protein in ovarian cancer multidrug resistance may be conducive to the development of human La protein-specific inhibitors that suppress ovarian cancer drug resistance.

Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency.

A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription.

Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation throughout mRNA lifespan with most impact on short tails.

La-related protein 4 (LARP4) directly binds both poly(A) and poly(A)-binding protein (PABP). LARP4 was shown to promote poly(A) tail (PAT) lengthening and stabilization of individual mRNAs presumably by protection from deadenylation (Mattijssen et al., 2017). We developed a nucleotide resolution transcriptome-wide, single molecule SM-PAT-seq method. This revealed LARP4 effects on a wide range of PAT lengths for human mRNAs and mouse mRNAs from LARP4 knockout (KO) and control cells. LARP4 effects are clear on long PAT mRNAs but become more prominent at 30-75 nucleotides. We also analyzed time courses of PAT decay transcriptome-wide and for ~200 immune response mRNAs. This demonstrated accelerated deadenylation in KO cells on PATs < 75 nucleotides and phasing consistent with greater PABP dissociation in the absence of LARP4. Thus, LARP4 shapes PAT profiles throughout mRNA lifespan with impact on mRNA decay at short lengths known to sensitize PABP dissociation in response to deadenylation machinery.

THU329 - Hepatic inflammation upregulates netrin-1 in mice and in vitro through translational activation and transcript topology alteration in a LA-related protein-1 (LARP1)-dependent manner

THU329 - Hepatic inflammation upregulates netrin-1 in mice and in vitro through translational activation and transcript topology alteration in a LA-related protein-1 (LARP1)-dependent manner

Transcriptome-wide stability analysis uncovers LARP4-mediated NFκB1 mRNA stabilization during Tcell activation.

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Motivated by our previous finding that intron retention (IR) could lead to transcript instability, in this study, we performed BruChase-Seq to experimentally monitor the expression dynamics of nascent transcripts in resting and activated CD4+ T cells. Computational modeling was then applied to quantify the stability of spliced and intron-retained transcripts on a genome-wide scale. Beyond substantiating that intron-retained transcripts were considerably less stable than spliced transcripts, we found a global stabilization of spliced mRNAs upon T cell activation, although the stability of intron-retained transcripts remained relatively constant. In addition, we identified that La-related protein 4 (LARP4), an RNA-binding protein (RBP) known to enhance mRNA stability, was involved in T cell activation-dependent mRNA stabilization. Knocking out Larp4 in mice destabilized Nfκb1 mRNAs and reduced secretion of interleukin-2 (IL2) and interferon-gamma (IFNγ), two factors critical for T cell proliferation and function. We propose that coordination between splicing regulation and mRNA stability may provide a novel paradigm to control spatiotemporal gene expression during T cell activation.

Circular RNA La-Related Protein 4 Inhibits Non-Small Cell Lung Cancer Cell Proliferation While Promotes Apoptosis Through Sponging microRNA-21-5p.

Background: This study aimed to investigate the function of circular RNA La-related protein 4 (circ-LARP4) on non-small cell lung cancer (NSCLC) progression. Materials and Methods: Circ-LARP4 overexpression and circ-LARP4 short hairpin RNA (shRNA) plasmids were transfected into NCI-H1650 cells and NCI-H1299 cells respectively. In rescue experiment, microRNA (miR)-21-5p overexpression and miR-21-5p shRNA plasmids were transfected into circ-LARP4 overexpression-treated NCI-H1650 cells and circ-LARP4 knockdown-treated NCI-H1650 cells, respectively. Circ-LARP4 and miR-21-5p expression levels were detected by reverse transcription-quantitative polymerase chain reaction. Cell proliferation and apoptosis were investigated by cell counting kit-8 assay and annexin V/propidium iodide assay. The interaction between circ-LARP4 and miR-21-5p was further explored by luciferase reporter assay. Results: Circ-LARP4 expression was decreased in NSCLC cell lines (including NCI-H1299, NCI-H522, NCI-H23, NCI-H358, and NCI-H1650) compared with human normal lung epithelial cell line. Circ-LARP4 overexpression inhibited cell proliferation while promoted apoptosis in NCI-H1650 cells, whereas circ-LARP4 knockdown increased cell proliferation while decreased apoptosis in NCI-H1299 cells. Meanwhile, miR-21-5p was negatively regulated by circ-LARP4, whereas circ-LARP4 was not affected by miR-21-5p in NCI-H1650 and NCI-H1299 cells. In rescue experiment, miR-21-5p overexpression attenuated the effect of circ-LARP4 overexpression on decreasing cell proliferation and increasing apoptosis in NCI-H1650 cells, whereas miR-21-5p knockdown attenuated the effect of circ-LARP4 knockdown on promoting cell proliferation and suppressing apoptosis in NCI-H1299 cells. Further luciferase reporter assay revealed that circ-LARP4 could directly bind to miR-21-5p. Conclusions: Circ-LARP4 is decreased and suppresses cell proliferation while promoted apoptosis by sponging miR-21-5p in NSCLC.

A-kinase-anchoring protein 1 (dAKAP1)-based signaling complexes coordinate local protein synthesis at the mitochondrial surface

Compartmentalization of macromolecules is a ubiquitous molecular mechanism that drives numerous cellular functions. The appropriate organization of enzymes in space and time enables the precise transmission and integration of intracellular signals. Molecular scaffolds constrain signaling enzymes to influence the regional modulation of these physiological processes. Mitochondrial targeting of protein kinases and protein phosphatases provides a means to locally control the phosphorylation status and action of proteins on the surface of this organelle. Dual-specificity protein kinase A anchoring protein 1 (dAKAP1) is a multivalent binding protein that targets protein kinase A (PKA), RNAs, and other signaling enzymes to the outer mitochondrial membrane. Many AKAPs recruit a diverse set of binding partners that coordinate a broad range of cellular processes. Here, results of MS and biochemical analyses reveal that dAKAP1 anchors additional components, including the ribonucleoprotein granule components La-related protein 4 (LARP4) and polyadenylate-binding protein 1 (PABPC1). Local translation of mRNAs at organelles is a means to spatially control the synthesis of proteins. RNA-Seq data demonstrate that dAKAP1 binds mRNAs encoding proteins required for mitochondrial metabolism, including succinate dehydrogenase. Functional studies suggest that the loss of dAKAP1-RNA interactions reduces mitochondrial electron transport chain activity. Hence, dAKAP1 plays a previously unappreciated role as a molecular interface between second messenger signaling and local protein synthesis machinery.

La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region.

Cell growth is a complex process shaped by extensive and coordinated changes in gene expression. Among these is the tightly regulated translation of a family of growth-related mRNAs defined by a 5' terminal oligopyrimidine (TOP) motif. TOP mRNA translation is partly controlled via the eukaryotic initiation factor 4F (eIF4F), a translation factor that recognizes the mRNA 5' cap structure. Recent studies have also implicated La-related protein 1 (LARP1), which competes with eIF4F for binding to mRNA 5' ends. However, it has remained controversial whether LARP1 represses TOP mRNA translation directly and, if so, what features define its mRNA targets. Here, we show that the C-terminal half of LARP1 is necessary and sufficient to control TOP mRNA translation in cells. This fragment contains the DM15 cap-binding domain as well as an adjacent regulatory region that we identified. We further demonstrate that purified LARP1 represses TOP mRNA translation in vitro through the combined recognition of both the TOP sequence and cap structure, and that its intrinsic repressive activity and affinity for these features are subject to regulation. These results support a model whereby the translation of TOP mRNAs is controlled by a growth-regulated competition between eIF4F and LARP1 for their 5' ends.

A La-Related Protein LaRP6a Delays Flowering of Arabidopsis thaliana by Upregulating FLC Transcript Levels

La-related proteins (LaRPs) are RNA-binding proteins (RBPs) that contain a La-type helix-turn-helix (HTH) domain and are found in all eukaryotes, including plants, animals, and yeasts. Although the functions of a few LaRPs have been determined during plant growth and development, the roles of most LaRPs in plants remain unknown. Here, the function of an Arabidopsis thaliana LaRP6a (At5g46250) harboring a La-type HTH domain and an RNA-recognition motif was determined in the growth and development of Arabidopsis. Confocal analysis of subcellular localization of the LaRP6a–GFP fusion protein revealed that LaRP6a protein is localized to both the nucleus and plasma membrane. Overexpression of LaRP6a resulted in delayed flowering and increased plant height and seed yield. The transcript level of the floral repressor FLC was markedly increased in LaRP6a-overexpressing transgenic plants. LaRP6a protein bound to the 3ʹUTR of the FLC transcript and possessed RNA chaperone activity. Collectively, these results suggest that LaRP6a plays a role in the control of flowering time by regulating FLC transcript levels.

The Structural Characterization of AtLaRP6a C‐Terminal Domain

The La related proteins (LaRPs) are a superfamily of RNA binding proteins characterized by a conserved sequence called the La Module. This domain is composed of two distinct regions, the La Motif (LAM) and an RNA recognition motif (RRM), which form a functional RNA binding unit. The LaRP6 subfamily is characterized by a putative protein‐protein interaction motif in the C‐terminus, called the LAM‐ and S1 associated (LSA) motif. Interestingly, plants express three paralogs of LaRP6 (A, B, and C). We have recombinantly expressed and purified the LaRP6A protein from the plant model organism Arabidopsis thaliana, to compare the plant LaRP6A to the LaRP6 proteins of vertebrate organisms for the purpose of probing differences in structure and function. Previous work in our lab suggested that the C‐terminal domain of AtLaRP6A is intrinsically disordered. In this study, we have recombinantly expressed and purified only the C‐terminal domain. Biochemical and biophysical analyses, including analytical size exclusion chromatography, limited proteolysis, and circular dichroism, all support the prediction that the CTD is an intrinsically disordered region. This work provides a foundation to further study the role of the CTD in regulatory protein‐protein interactions to better understand the biological role for LaRP6.

Effect of the N‐terminal Region of Arabidopsis thaliana LARP6C in RNA Binding Specificity

The La‐related proteins (LARPs) are a superfamily of RNA‐binding proteins that are distinguished by a core RNA binding domain called the “La Module”. This family is highly conserved across eukaryotes and exerts diverse functions in RNA processing and function. The genetic model vascular plant, Arabidopsis thaliana (At), has three paralogs of LARP6, denoted “A”, “B”, and “C”. Of these paralogs, AtLARP6B and AtLARP6C are more closely related to each other due to an N‐terminal sequence motif known to associate with other RNA binding proteins, the “PAM2w” motif. Previous work evaluated the RNA binding activity of the isolated AtLARP6C La Module. Recent work on vertebrate LARP4A suggests that N‐terminal PAM2 motifs are important for higher‐order assembly of regulatory complexes. We have generated a set of recombinant constructs to test the role of both the NTR and PAM2w motif in RNA binding activity. These protein variants are stably expressed and have been highly purified for use in electrophoretic mobility shift assays (EMSAs) to measure RNA binding activity. Preliminary work indicates that binding affinity is not significantly impacted by either the NTR or the PAM2w motif, and current studies are focusing on the role that these regions play in ligand specificity. By characterizing the binding specificity of these AtLARP6C proteins to a panel of RNA ligands, we will gain significant insight into the contribution of this domain and motif to ligand binding.

Distribution, organization an evolutionary history of La and LARPs in eukaryotes

ABSTRACT The fate of any cellular RNA is largely influenced by the nature and diversity of its interactions with various RNA-binding proteins (RBPs) leading to the formation of a biologically significant ribonucleoprotein (RNP) complex. La motif-containing proteins (composed of genuine La and La-related proteins (LARPs)) represent an evolutionary conserved family of RBPs that encompass a large range of crucial functions, involving coding and non-coding RNAs. In this work, we provide data that extend our previous knowledge on the distribution, organization and evolutionary history of this important protein family. Using a repertoire of 345 La motif-containing proteins from 135 species representing all major eukaryotic lineages, we were able to pinpoint many lineage-specific variations in the structural organization of La and LARPs and propose new evolutive scenarios to explain their modern genomic distribution.

Structural dynamics in the La-module of La-related proteins

ABSTRACT The La-related proteins (LaRPs) are a superfamily of eukaryotic RNA-binding proteins with important and varied roles. To understand LaRP functions it is essential to unravel the divergent features responsible for their RNA target selectivity, which underlie their distinct identities and cellular roles. LaRPs are built on a common structural module called the ‘La-module’ that acts as a main locus for RNA recognition. The La-module is comprised of two tethered domains whose relative structural and dynamic interplay has been proposed to regulate RNA-target selection, albeit the mechanistic underpinning of this recognition remains to be elucidated. A main unsolved conundrum is how conserved La-modules across LaRPs are able to bind to extremely diverse RNA ligands. In this work, we employed Small Angle X-ray Scattering (SAXS) to investigate several human LaRP La-modules in the absence and, where applicable, in the presence of their RNA target, with the aim to explore the structural dynamics of their RNA recognition and provide information on the architectural landscape accessible to these proteins. Integration of these SAXS experiments with prior X-ray crystallography and NMR data suggests that RNA binding is generally accompanied by a compaction and loss of flexibility of the La-module. Nonetheless, the La-modules appear to experience a considerably different degree of inherent flexibility in their apo state. Furthermore, although they all exist in discrete subsets of accessible populations in equilibrium, these vary from LaRP to LaRP and can be either extended or compact. We propose that these divergent features may be critical for RNA substrate discrimination.

Circular RNA La-related RNA-binding protein 4 correlates with reduced tumor stage, as well as better prognosis, and promotes chemosensitivity to doxorubicin in breast cancer.

ObjectiveWe aimed to evaluate the correlation of circular RNA La‐related RNA‐binding protein 4 (circ‐LARP4) with tumor characteristics and prognosis, and its effect on chemosensitivity in breast cancer.MethodsCirc‐LARP4 from tumor and adjacent tissues of 283 female breast cancer patients underwent resection was detected by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Tumor features, disease‐free survival (DFS), and overall survival (OS) were recorded. In vitro, circ‐LARP4 in human normal mammary epithelial cells (HMEC) and breast cancer cell lines was detected by RT‐qPCR. MCF‐7 and MDA‐MB‐231 cells were transfected with circ‐LARP4 overexpression plasmid (as OE‐Circ group) and control overexpression plasmid (as OE‐Control group). Relative cell viability under different concentrations of doxorubicin was measured.ResultsCirc‐LARP4 was decreased in tumor tissues than adjacent tissues (P < .001). Tumor circ‐LARP4 negatively correlated with tumor size (P = .001), T stage (P = .009), N stage (P = .006), and TNM stage (P < .001), whereas positively correlated with DFS (P = .004) and OS (P < .001). In vitro, circ‐LARP4 was decreased MCF‐7, BT474, MDA‐MB‐231, and MDA‐MB‐468 cell lines than HMEC (all P < .001). Relatively cell viability of MCF‐7 cells (at 20 nmol/L [P < .05], 40 nmol/L [P < .01], 80 nmol/L [P < .05] of doxorubicin) and MDA‐MB‐231 cells (at 120 nmol/L [P < .05], 240 nmol/L [P < .05] of doxorubicin) was decreased in OE‐Circ group than OE‐Control group. IC50 value of doxorubicin was decreased in OE‐Circ group than OE‐Control group in MCF‐7 and MDA‐MB‐231 cell lines (both P < .01).ConclusionCirc‐LARP4 was a potential prognostic biomarker, which might improve the management of breast cancer.