Functional and Structural Aspects of La Protein Overexpression in Lung Cancer

Kaliatsi, Eleni G.; Argyriou, Aikaterini I.; Bouras, Georgios; Apostolidi, Maria; Konstantinidou, Parthena; Shaukat, Athanasios-Nasir; Spyroulias, Georgios A.; Stathopoulos, Constantinos

doi:10.1016/j.jmb.2020.11.011

Cited by 4 publications

(7 citation statements)

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“…The crystal structure of the "La Module" in complex with RNA oligos was also determined and reported in the literature (PDB ID: 2VOD, 2VOO, 2VOP, 2VON, 1ZH5 and 1YTY) [9][10][11]22,23]. In addition, we have determined that the La motif alone is capable of binding precursor tRNAs, which are among the in vivo ligands of the La protein [7]. Interestingly, the recent demonstration of an La protein representative in a Tetrahymena that lacks any recognizable RRM motif confirms previous observations and underlines the necessity of studying the individual domains and modules of the La protein in their biological context [24].…”

Section: Introductionmentioning

confidence: 88%

“…The La protein binds the 3 end of all pre-mature Pol III transcripts to assist proper folding and subsequent maturation. Due to its role in transcription regulation, the La protein is mainly localized in the nucleus, though in specific cases it can shuttle to the cytoplasm and interact with a variety of different mRNAs (endogenous and viral) to stimulate their translation [5][6][7]. For example, it was reported recently that La overexpression can stimulate cap-independent translation through direct binding on the IRES of reporter genes [7].…”

Section: Introductionmentioning

confidence: 99%

“…Due to its role in transcription regulation, the La protein is mainly localized in the nucleus, though in specific cases it can shuttle to the cytoplasm and interact with a variety of different mRNAs (endogenous and viral) to stimulate their translation [5][6][7]. For example, it was reported recently that La overexpression can stimulate cap-independent translation through direct binding on the IRES of reporter genes [7]. Interestingly, it was also reported that the La protein acts as the gatekeeper for specific pre-tRNAs, to prevent their processing by Dicer for the production of specific miRNAs [8].…”

Section: Introductionmentioning

confidence: 99%

“…Given the important cellular role of the La protein and the fact that absence of the La protein causes disruption of the nucleolar organization, the recognition of various RNA structured domains by the La protein as a whole or through synergy between its different modules still awaits clarification [7]. The solution structures of each domain (LaM PDB ID:1S7A, RRM1 PDB ID: 1S79 and RRM2 PDB ID: 1OWX) have been individually determined through NMR.…”

Section: Introductionmentioning

confidence: 99%

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NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

Argyriou

Machaliotis

Makrynitsa

et al. 2023

IJMS

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The La protein (lupus antigen) is a ubiquitous RNA-binding protein found in all human cells. It is mainly localized in the nucleus, associates with all RNA polymerase III (Pol III) transcripts, as the first factor they interact with, and modulates subsequent processing events. Export of La to the cytoplasm has been reported to stimulate the decoding of specific cellular and viral mRNAs through IRES-dependent (Internal ribosome entry site) binding and translation. Using NMR (Nuclear Magnetic Resonance) spectroscopy, we provide atomic-level-resolution structural insights on the dynamical properties of human La (hLa) protein in solution. Moreover, using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we provide evidence about the role and ligand specificity of the C-terminal domain of the La protein (RRM2 and C-terminal region) that could mediate the recognition of HCV-IRES.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

Argyriou

Machaliotis

Makrynitsa

et al. 2023

IJMS

Self Cite

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“…La protein is highly expressed in various malignant tumors, and its expression is related to the clinical TNM stage, lymph node metastasis, and differentiation degree of tumor cells, which plays an important role in the translation control of tumor promoters ( 10 – 13 ). It can promote the tumorigenicity, change the cell cycle, and promote the proliferation, migration, and invasion of cancer cells ( 12 , 14 , 15 ). It can also promote the translation of Bcl-2, which may promote drug resistance by inhibiting the apoptosis of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

Huang

Zhu

et al. 2022

Front. Oncol.

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Research on the mechanism and new targets of ovarian cancer is of great significance to reduce the high mortality and drug resistance of ovarian cancer. Human La protein has been found to be highly expressed in a variety of malignant tumors and plays a role in tumorigenesis and development through its RNA-binding function. However, its role and mechanism in ovarian cancer are not completely clear. The present study showed that La protein was highly expressed in serum and tissues of patients with ovarian cancer by ELISA and immunohistochemistry, and the high expression of La protein was associated with the increased degree of malignancy and poor prognosis by searching the KM plotter database. Interference of the La gene resulted in a significant decrease in the proliferation, migration, and invasion of ovarian cancer cells with growth block in the G1 phase and increasing apoptosis. By RNA binding protein immunoprecipitation, transcriptome sequencing, and proteomics, 14 downstream target genes were screened. The La protein might affect the protein expression of these 14 genes by binding with the mRNAs. Therefore, it played a role in the pathological process of ovarian cancer.

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RNA-based therapies: A cog in the wheel of lung cancer defense

et al. 2021

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Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies.

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Functional and Structural Aspects of La Protein Overexpression in Lung Cancer

Cited by 4 publications

References 60 publications

NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

RNA-based therapies: A cog in the wheel of lung cancer defense

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