LARP1

Official Full Name

La ribonucleoprotein 1, translational regulator

Organism

Homo sapiens

GeneID

23367

Background

Enables eukaryotic initiation factor 4E binding activity; nucleic acid binding activity; and ribosomal small subunit binding activity. Involved in several processes, including TORC1 signaling; cellular response to rapamycin; and post-transcriptional regulation of gene expression. Located in TORC1 complex and cytoplasmic stress granule. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

LARP; Lar1; Lhp1;

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Detailed Information

Recent Progress

RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression of the protein in hepatocellular and lung cancers is correlated with adverse prognosis. LARP1 is a conserved RBP that interacts with poly-A-binding protein and is known to regulate N-terminal oligopyrimidine tract (TOP) mRNA translation (Fig.1). These LARP1 proteins form an evolutionarily homogeneous subgroup of the eukaryotic superfamily of La-Motif (LAM) containing factors. Members of the LARP1 family are found in most fungi, plants, and animals. There has been evidence suggesting that LARP1 are key versatile messenger RNA (mRNA)-binding proteins involved in regulating important biological processes such as gametogenesis, embryogenesis, sex determination, and cell division in animals, as well as acclimation to stress. LARP1 proteins perform all these essential tasks likely by binding to key mRNAs and regulating their stability and translation. In human, the impact of LARP1 over cell division and proliferation is potentially under the control of the TORC1 complex. Previous data suggested that LARP1 is a direct target of this master signaling hub. TOR-dependent LARP1 phosphorylation could specifically enhance the translation of TOP mRNAs, providing an approach to promote translation, growth, and proliferation.

Fig. 1. LARP1 specifically recognized the 3′ terminus of a poly(A) tail. (Deragon et al, 2015)

In another study, it was shown that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR, whose mRNA transcript is stabilized by LARP1. At the functional level, it was previously shown that LARP1 could promote cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, researchers indicated that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. Therefore, it was concluded that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

In one study, researchers explored the role of LARP1 in epithelial ovarian cancer, a disease characterized by the rapid acquisition of resistance to chemotherapy. Using ovarian cell lines and xenografts, researchers were able to show that LARP1 is required for cancer cell survival and chemotherapy resistance. LARP1 promoted tumor formation in vivo and maintained cancer stem cell-like populations. Using transcriptomic analysis following LARP1 knockdown, investigators identified BCL2 and BIK as LARP1 mRNA targets. It was also demonstrated that, through an interaction with the 3' untranslated regions (3' UTRs) of BCL2 and BIK, LARP1 stabilized BCL2 but destabilized BIK with the net effect of resisting apoptosis. Together, these data indicated that by differentially regulating the stability of a selection of mRNAs, LARP1 can promote ovarian cancer progression and chemotherapy resistance.

Another study investigated the significance of LARP1 in the development and progression of colorectal cancer (CRC). CRC tumor tissues and paired adjacent normal mucosa were studied. The expression of LARP1 was upregulated in CRC. Through immunohistochemical analysis, a positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed. The inhibitory effect of LARP1 knockdown on CRC cell proliferation was also demonstrated. Further analysis showed that LARP1 was an independent prognostic factor for overall survival and disease-free survival in CRC patients. Taken together, these findings suggested that LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.

References:

Deragon, J. M., & Bousquetantonelli, C. (2015). The role of larp1 in translation and beyond. Wiley Interdisciplinary Reviews-rna, 6(4), 399–417.
Mura, M., Hopkins, T. G., Michael, T., Abdlatip, N., Weir, J., & Aboagye, E., et al. (2015). Larp1 post-transcriptionally regulates mtor and contributes to cancer progression. Oncogene, 34(39), 5025-5036.
Hong, S., Freeberg, M. A., Han, T., Kamath, A., Yao, Y., & Fukuda, T., et al. (2017). Larp1 functions as a molecular switch for mtorc1-mediated translation of an essential class of mrnas. eLife,6,(2017-06-15), 6.
Lahr, R. M., Fonseca, B. D., Ciotti, G. E., Alashtal, H. A., Jia, J. J., & Niklaus, M. R., et al. (2017). La-related protein 1 (larp1) binds the mrna cap, blocking eif4f assembly on top mrnas. eLife,6,(2017-04-04), 6.
Hopkins, T. G., Mura, M., Alashtal, H. A., Lahr, R. M., Abdlatip, N., & Sweeney, K., et al. (2016). The rna-binding protein larp1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer. Nucleic Acids Research, 44(3), 1227.
Ye, L., Lin, S. T., Mi, Y. S., Liu, Y., Ma, Y., & Sun, H. M., et al. (2016). Overexpression of larp1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target. Tumour Biology, 37(11), 14585-14594.

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