PNO1

Last update 23 Jan 2025

Basic Info

Synonyms

KHRBP1, Partner of NOB1, partner of NOB1 homolog

+ [3]

Introduction

Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA (PubMed:25851604).

100 Clinical Results associated with PNO1

100 Translational Medicine associated with PNO1

0 Patents (Medical) associated with PNO1

Literatures (Medical) associated with PNO1

01 Oct 2024·Journal of Immunotherapy

Increased Expression and Prognostic Significance of BYSL in Melanoma

Article

Author: Zhu, Yuan-jie ; Wang, Liang-zhe ; Wang, Zhong-zhi ; Chen, Jiang-han ; Yao, Guo-tai

We evaluated the BYSL content and underlying mechanism in melanoma (SKCM) overall survival (OS). In this study, we used a comprehensive approach combining bioinformatics tools, including miRNA estimation, quantitative real-time polymerase chain reaction (qRT-PCR) of miRNAs, E3 ligase estimation, STRING analysis, TIMER analysis, examination of associated upstream modulators, protein-protein interaction (PPI) analysis, as well as retrospective and survival analyses, alongside clinical sample validation. These methods were used to investigate the content of BYSL, its methylation status, its relation to patient outcome, and its immunologic significance in tumors. Our findings revealed that BYSL expression is negatively regulated by BYSL methylation. Analysis of 468 cases of SKCM RNA sequencing samples demonstrated that enhanced BYSL expression was associated with higher tumor grade. We identified several miRNAs, namely hsa-miR-146b-3p, hsa-miR-342-3p, hsa-miR-511-5p, hsa-miR-3690, and hsa-miR-193a-5p, which showed a strong association with BYSL levels. Furthermore, we predicted the E3 ubiquitin ligase of BYSL and identified CBL, FBXW7, FZR1, KLHL3, and MARCH1 as potential modulators of BYSL. Through our investigation, we discovered that PNO1, RIOK2, TSR1, WDR3, and NOB1 proteins were strongly associated with BYSL expression. In addition, we found a close association between BYSL levels and certain immune cells, particularly dendritic cells (DCs). Notably, we observed a significant negative correlation between miR-146b-3p and BYSL mRNA expression in SKCM sera samples. Collectively, based on the previously shown evidences, BYSL can serve as a robust bioindicator of SKCM patient prognosis, and it potentially contributes to immune cell invasion in SKCM.

01 Oct 2024·Current Pharmaceutical Design

Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms

Review

Author: Ragunath, Muthu ; Shen, Aling ; Peng, Jun ; Thiruvengadam, Muthu ; Wei, Lin

: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.

21 Sep 2024·Journal of Biomolecular Structure and Dynamics

A comprehensive identification of potential molecular targets and small drugs candidate for melanoma cancer using bioinformatics and network-based screening approach.

Article

Author: Sultana, Mst Tania ; Adhikary, Tonmoy ; Khan, Dhrubo Ahmed ; Toukir, Imran Ahamed

Melanoma is the third most common malignant skin tumor and has increased in morbidity and mortality over the previous decade due to its rapid spread into the bloodstream or lymphatic system. This study used integrated bioinformatics and network-based methodologies to reliably identify molecular targets and small molecular medicines that may be more successful for Melanoma diagnosis, prognosis and treatment. The statistical LIMMA approach utilized for bioinformatics analysis in this study found 246 common differentially expressed genes (cDEGs) between case and control samples from two microarray gene-expression datasets (GSE130244 and GSE15605). Protein-protein interaction network study revealed 15 cDEGs (PTK2, STAT1, PNO1, CXCR4, WASL, FN1, RUNX2, SOCS3, ITGA4, GNG2, CDK6, BRAF, AGO2, GTF2H1 and AR) to be critical in the development of melanoma (KGs). According to regulatory network analysis, the most important transcriptional and post-transcriptional regulators of DEGs and hub-DEGs are ten transcription factors and three miRNAs. We discovered the pathogenetic mechanisms of MC by studying DEGs' biological processes, molecular function, cellular components and KEGG pathways. We used molecular docking and dynamics modeling to select the four most expressed genes responsible for melanoma malignancy to identify therapeutic candidates. Then, utilizing the Connectivity Map (CMap) database, we analyzed the top 4-hub-DEGs-guided repurposable drugs. We validated four melanoma cancer drugs (Fisetin, Epicatechin Gallate, 1237586-97-8 and PF 431396) using molecular dynamics simulation with their target proteins. As a result, the results of this study may provide resources to researchers and medical professionals for the wet-lab validation of MC diagnosis, prognosis and treatments.Communicated by Ramaswamy H. Sarma.

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PNO1

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