LARP1 specifically recognizes the 3′ terminus of poly(A) mRNA

Aoki, Kai; Adachi, Shungo; Homoto, Masae; Kusano, Hideo; Koike, Kazuyuki; Natsume, Tohru

doi:10.1016/j.febslet.2013.05.035

Cited by 94 publications

(151 citation statements)

References 25 publications

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“…5B). These results confirm the previously reported stimulatory effect of these LARPs on gene expression (Burrows et al 2010;Schäffler et al 2010;Yang et al 2011;Aoki et al 2013;Mura et al 2014;Tcherkezian et al 2014). The simultaneous knockdown of LARP4 and LARP4B led to a decrease in the luciferase activity by 55%.…”

Section: Larp4b Larp4 and Larp1 Interact With An Overlapping Set Ofsupporting

confidence: 91%

“…Similar biochemical and functional properties were reported for LARP4B, LARP4, and LARP1. They are cytoplasmic proteins that translocate into stress granules under cellular stress conditions, interact with PABPC1, associate with actively translating ribosomes and exert stabilizing effects on target mRNAs (Burrows et al 2010;Schäffler et al 2010;Yang et al 2011;Aoki et al 2013;Mura et al 2014;Tcherkezian et al 2014). This suggests that they might fulfill overlapping or redundant functions in mRNA metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, members of the LARP3 and LARP7 families associate predominantly with RNA polymerase III (RNAPIII) transcripts in vivo and influence their stability and/or maturation pathways (Sobel and Wolin 1999;Intine et al 2000;Aigner et al 2003;Chakshusmathi et al 2003;Aigner and Cech 2004;Prathapam et al 2005;Stone et al 2007;Copela et al 2008;Krueger et al 2008;Markert et al 2008). While other LARP family members also contain La modules, recent evidence suggested that LARP1, LARP4, and LARP6 are associated with mRNAs rather than RNAPIII transcripts (Nykamp et al 2008;Blagden et al 2009;Wang et al 2009;Weng et al 2009;Burrows et al 2010;Cai et al 2010a;Schäffler et al 2010;Zanin et al 2010;Yang et al 2011;Aoki et al 2013;Mura et al 2014;Tcherkezian et al 2014). LARP6 has been shown to interact with a hairpin structure located in the 5 ′ untranslated region (UTR) of the mRNA encoding collagen.…”

Section: Introductionmentioning

confidence: 99%

“…LARP1 has been shown to associate with many cytoplasmic mRNPs, primarily via interactions with translation factors including the poly(A)-binding protein PABPC1 but also via RNA sequences (Blagden et al 2009;Burrows et al 2010;Aoki et al 2013;Mura et al 2014;Tcherkezian et al 2014). LARP1 has recently attracted major attention as it acts in the mTORC1 pathway to control the translation and stability of mRNAs containing the 5 ′ terminal oligopyrimidine tract (TOP) motif (Aoki et al 2013;Tcherkezian et al 2014). These TOP-mRNAs encode mostly factors of the translation machinery (i.e., ribosomal proteins and translation factors), thus putting the control of this class of mRNAs to the heart of cell growth and proliferation.…”

Section: Introductionmentioning

confidence: 99%

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LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation

Küspert

Murakawa

Schäffler

et al. 2015

RNA

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mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level. The Larelated protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA-binding proteins characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown previously direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3 ′ UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B-binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability.

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Section: Larp4b Larp4 and Larp1 Interact With An Overlapping Set Ofsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation

Küspert

Murakawa

Schäffler

et al. 2015

RNA

View full text Add to dashboard Cite

show abstract

“…72 This protein was previously shown to associate with and promote the stability of TOP mRNAs, 73 suggesting that LARP1 may regulate TOP mRNAs at different levels to control their expression in cells. Interestingly, 2 studies aiming to characterize the mTOR phosphoproteome repertoire have identified LARP1 as a potential mTORC1 phosphorylation substrate.…”

Section: Translational Control Of Top Mrnasmentioning

confidence: 99%

Regulation of global and specific mRNA translation by the mTOR signaling pathway

2015

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O‐GlcNAcylated LARP1 positively regulated by circCLNS1A facilitates hepatoblastoma progression through DKK4/β‐catenin signalling

Cui

Zhu

et al. 2023

Clinical & Translational Med

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Background Accumulating studies have shown that La‐related protein 1 (LARP1) is involved in the occurrence and development of various tumours. However, the expression pattern and biological role of LARP1 in hepatoblastoma (HB) remain unclear so far. Methods LARP1 expression level in HB and adjacent normal liver tissues was analysed by qRT‐PCR, Western blotting and immunohistochemistry assays. The prognostic significance of LARP1 was evaluated by Kaplan–Meier method and multivariate Cox regression analysis. In vitro and in vivo functional assays were implemented to clarify the biological effects of LARP1 on HB cells. Mechanistically, the regulatory roles of O‐GlcNAcylation and circCLNS1A in LARP1 expression were investigated by co‐immunoprecipitation (co‐IP), immunofluorescence, RNA immunoprecipitation (RIP), RNA pull‐down and protein stability assays. Moreover, RNA‐sequencing, co‐IP, RIP, mRNA stability and poly(A)‐tail length assays were performed to investigate the association between LARP1 and DKK4. The expression and diagnostic significance of plasma DKK4 protein in multi‐centre cohorts were evaluated by ELISA and ROC curves. Results LARP1 mRNA and protein levels were remarkably elevated in HB tissues and associated with worse prognosis of HB patients. LARP1 knockdown abolished cell proliferation, triggered cell apoptosis in vitro as well as prohibited tumour growth in vivo, whereas LARP1 overexpression incited HB progression. Mechanistically, O‐GlcNAcylation of LARP1 Ser672 by O‐GlcNAc transferase strengthened its binding to circCLNS1A and then protected LARP1 from TRIM‐25‐mediated ubiquitination and proteolysis. LARP1 upregulation subsequently led to DKK4 mRNA stabilisation by competitively interacting with PABPC1 to prevent DKK4 mRNA from B‐cell translocation gene 2‐dependent deadenylation and degradation, thus facilitating β‐catenin protein expression and nuclear import. Conclusion This study indicates that upregulated protein level of O‐GlcNAcylated LARP1 mediated by circCLNS1A promotes the tumorigenesis and progression of HB through LARP1/DKK4/β‐catenin axis. Hence, LARP1 and DKK4 are promising therapeutical target and diagnostic/prognostic plasma biomarker for HB.

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LARP1 specifically recognizes the 3′ terminus of poly(A) mRNA

Cited by 94 publications

References 25 publications

LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation

LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation

Regulation of global and specific mRNA translation by the mTOR signaling pathway

O‐GlcNAcylated LARP1 positively regulated by circCLNS1A facilitates hepatoblastoma progression through DKK4/β‐catenin signalling

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