The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease

Catalanotto, Caterina; Barbato, Christian; Cogoni, Carlo; Benelli, Dario

doi:10.3390/biomedicines11112969

Cited by 3 publications

(1 citation statement)

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“…The abundance of RNA and proteins in a cell is the outcome of the balance between their production and degradation, that are regulated by the gene expression control system ( Jolma et al, 2020 ). The relationship between proteins and RNA, which dates back to the discovery of ribosomes, is strongly entwined and coordinated, and witnesses the ancient and dynamic interaction between ribosomal RNA (rRNA) and ribosomal proteins to regulate translation ( Palade, 1955 ; Catalanotto et al, 2023 ). Post-transcriptional regulation of gene expression takes place at different levels: RNA splicing and editing, stability and decay, translocation and localization as well as translation, which are mostly under the control of RNA-binding proteins (RBPs).…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Ala,

Fagoonee

2024

Front. Mol. Biosci.

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Primary Sclerosing Cholangitis (PSC) is a persistent inflammatory liver condition that affects the bile ducts and is commonly diagnosed in young individuals. Despite efforts to incorporate various clinical, biochemical and molecular parameters for diagnosing PSC, it remains challenging, and no biomarkers characteristic of the disease have been identified hitherto. PSC is linked with an uncertain prognosis, and there is a pressing need to explore multiomics databases to establish a new biomarker panel for the early detection of PSC’s gradual progression into Cholangiocarcinoma (CCA) and for the development of effective therapeutic interventions. Apart from non-coding RNAs, other components of the Ribonucleoprotein (RNP) complex, such as RNA-Binding Proteins (RBPs), also hold great promise as biomarkers due to their versatile expression in pathological conditions. In the present review, an update on the RBP transcripts that show dysregulated expression in PSC and CCA is provided. Moreover, by utilizing a bioinformatic data mining approach, we give insight into those RBP transcripts that also exhibit differential expression in liver and gall bladder, as well as in body fluids, and are promising as biomarkers for diagnosing and predicting the prognosis of PSC. Expression data were bioinformatically extracted from public repositories usingTCGA Bile Duct Cancer dataset for CCA and specific NCBI GEO datasets for both PSC and CCA; more specifically, RBPs annotations were obtained from RBP World database. Interestingly, our comprehensive analysis shows an elevated expression of the non-canonical RBPs, FANCD2, as well as the microtubule dynamics regulator, ASPM, transcripts in the body fluids of patients with PSC and CCA compared with their respective controls, with the same trend in expression being observed in gall bladder and liver cancer tissues. Consequently, the manipulation of tissue expression of RBP transcripts might be considered as a strategy to mitigate the onset of CCA in PSC patients, and warrants further experimental investigation. The analysis performed herein may be helpful in the identification of non-invasive biomarkers for the early detection of PSC and for predicting its progression into CCA. In conclusion, future clinical research should investigate in more depth the full potential of RBP transcripts as biomarkers for human pathologies.

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Section: Introductionmentioning

confidence: 99%

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Ala,

Fagoonee

2024

Front. Mol. Biosci.

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Long noncoding RNAs in ubiquitination, protein degradation, and human diseases

Guha,

Chini,

Rishi

et al. 2024

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms

Ragunath,

Shen,

Wei

et al. 2024

CPD

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Post-transcriptional modifications (PTMs) are pivotal in the regulation of gene expression, and pseudouridylation is emerging as a critical player. This modification, facilitated by enzymes such as NOB1 (PNO1), is integral to ribosome biogenesis. PNO1, in collaboration with the NIN1/RPN12 binding protein 1 homolog (NOB1), is vital for the maturation of ribosomes, transitioning 20S pre-rRNA into functional 18S rRNA. Recent studies have highlighted PNO1's potential involvement in cancer progression; however, its underlying mechanisms remain unclear. Relentless growth characterizing cancer underscores the burgeoning significance of epitranscriptomic modifications, including pseudouridylation, in oncogenesis. Given PNO1's emerging role, it is imperative to delineate its contribution to cancer development to identify novel therapeutic interventions. This review summarizes the current literature regarding the role of PNO1 in cancer progression and its molecular underpinnings in oncogenesis. Overexpression of PNO1 was associated with unfavorable prognosis and increased tumor malignancy. At the molecular level, PNO1 facilitates cancer progression by modulating mRNA stability, alternative splicing, and translation efficiency. Its role in pseudouridylation of oncogenic and tumor-suppressor transcripts further underscores its significance in cancer biology. Although disruption of ribosome biogenesis is known to precipitate oncogenesis, the precise mechanisms by which these alterations contribute to cancer remain unclear. This review elucidates the intricate process of ribosomal small subunit maturation, highlighting the roles of crucial ribosomal proteins (RPs) and RNA-binding proteins (RBPs) as well as the positioning and function of NOB1 and PNO1 within the 40S subunit. The involvement of these components in the maturation of the small subunit (SSU) and their significance in the context of cancer therapeutics has been thoroughly explored. PNO1's burgeoning significance in oncology makes it a potential target for cancer therapies. Strategies aimed at modulating PNO1-mediated pseudouridylation may provide new avenues for cancer treatment. However, further research is essential to unravel the complete spectrum of PNO1 mechanisms in cancer and harness this knowledge for the development of targeted and more efficacious anticancer therapies.

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The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease

Cited by 3 publications

References 157 publications

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Long noncoding RNAs in ubiquitination, protein degradation, and human diseases

Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms

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