The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109288 - 109288

Published: Feb. 24, 2024

Language: Английский

---

The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

LARP4 interacts with poly(A)-binding protein (PABP) to protect messenger RNAs (mRNAs) from deadenylation and decay, recent data indicate it can direct the translation of functionally related mRNA subsets. was known bind RACK1, a ribosome-associated protein, although specific regions involved relevance had been undetermined. Here, through combination in-cell in vitro methodologies, we identified positions 615-625 conserved region-2 (CR2) (and 646-656 LARP4B) as directly binding RACK1. Consistent these results, AlphaFold2-Multimer predicted high-confidence interaction CR2 RACK1 propellers 5 6. mutations strongly decreased association cellular ribosomes by multiple assays, whereas PABP less affected, consistent independent interactions. The LARP4's ability stabilize β-globin reporter containing an AU-rich element (ARE) higher degree than GFP (green fluorescent protein) mRNAs lacking ARE. We show robustly increases β-glo-ARE mRNA, mutant is impaired. Analysis nanoLuc-ARE for production luciferase activity confirmed promotes efficiency, while are disabling. Thus, CR2-mediated promote translational efficiency some mRNAs.

Language: Английский

---

1H, 13C, and 15N resonance assignment of the 5’SL-bound La domain of the human La-related protein 6

Biomolecular NMR Assignments, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Language: Английский

---

LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function

RNA, Journal Year: 2023, Volume and Issue: 30(3), P. 223 - 239

Published: Dec. 20, 2023

Mitochondria-associated RNA-binding proteins (RBPs) have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out identify RBPs that regulate nuclear-encoded mRNAs (NEMmRNAs). Our systematic analysis of RNA targets 150 identified with a preference for binding NEMmRNAs, including LARP4, La RBP family member. We show LARP4's are particularly enriched in encode respiratory chain complex (RCCPs) ribosome (MRPs) across multiple human cell lines. Through quantitative proteomics, demonstrate depletion LARP4 leads significant reduction RCCP MRP protein levels. Furthermore, reduces function, re-expression rescues this phenotype. findings shed light on novel function an binds positively regulates NEMmRNAs promote function.

Language: Английский

---

The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

ABSTRACT LARP4 interacts with poly(A)-binding protein (PABP) to protect mRNAs from deadenylation and decay, recent data indicate it can direct the translation of functionally related mRNA subsets. was known bind RACK1, a ribosome-associated protein, although specific regions involved, relevance had been undetermined. Here, yeast two-hybrid domain mapping followed by other methods identified positions 615-625 in conserved region-2 (CR2) (and LARP4B) as directly binding RACK1 region 200-317. Consistent these results, AlphaFold2-multimer predicted high confidence interaction CR2 propellers 5-6. mutations strongly decreased association cellular ribosomes multiple assays, whereas less effect observed for PABP association, consistent independent interactions. ability optimally stabilize β-globin reporter containing an AU-rich element (ARE) more significantly than reporters lacking this element. While polysome profiles β-glo-ARE is inefficiently translated, published data, we show that increases its LARP4-CR2 mutant impaired. Analysis nanoLuc-ARE production luciferase activity confirmed promotes efficiency while are disabling. Thus, CR2-mediated promote translational some mRNAs.

Language: Английский

---

Overexpression of lncRNA LINC00294 Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer by Regulating the miR‐499a‐5p/LARP4B Axis

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 39(1)

Published: Dec. 24, 2024

Increasing long noncoding RNAs (lncRNAs) have been found to participate in regulating the progression of colorectal cancer (CRC), which is a common gastrointestinal malignancy. Here, specific role and mechanisms lncRNA LINC00294 were investigated CRC. The expression levels LINC00294, miR-499a-5p, La-related protein 4B (LARP4B) CRC cells (HCT116 SW620) tissues assessed by RT-qPCR. viability, proliferation, cell cycle, apoptosis HCT116 SW620 determined CCK-8, EdU, flow cytometry assays. Protein cycle markers measured western blot analysis. FISH assay was performed evaluate subcellular localization cells. Luciferase reporter assay, RNA pull-down as well RIP verified interactions between miR-499a-5p (or LARP4B). xenograft model established mice investigate function vivo. presented decreased level tissues. overexpression suppressed proliferative capacity, promoted arrest, induced interacted with targeted LARP4B. MiR-499a-5p upregulated while LARP4B downregulated In rescue assays, knockdown reversed inhibition on malignant phenotypes model, inhibited tumor growth exerted an antitumor forming LINC00294/miR-499a-5p/LARP4B regulatory network.

Language: Английский

---