Ribosome biogenesis in disease: new players and therapeutic targets

Abstract

The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

The longest intron rule

“…In current works on ribosomal proteins, their other functions beyond the framework of ribosome formation and maintenance are emphasized, e.g. activation of p53-dependent pathway in response to stress [26,27]. Thus, the significance of the longest intron feature of these genes highlighted by us may also turn out to be broader and awaits further investigation.…”

The Identification of Hub Genes in Diagnosing Blunt Trauma with Venous Thromboembolism Using Integrated Bioinformatic Analysis

“…using mRNA as a template, and using amino acids as raw materials to synthesize proteins, is the ribosome's primary function (24). Previous studies have showed that the ribosome has a great deal of functions, including affecting protein synthesis and taking a signi cant role in cell differentiation, proliferation, transformation and apoptosis (25). VTE may be diagnosed and treated by using ribosomal protein family genes(26).…”

The value of RPS15 and MRPS27 in ischemic stroke

“…Ribosomal biogenesis, translation, and defects in the function of a single RP (including mutations in RP) have been associated with a variety of human congenital diseases called ribosomal diseases. [16][17][18] Studies have shown that ribosomal protein families regulate the expression of oncogenes and tumor suppressor genes, regulate cell cycle and apoptosis, promote angiogenesis, cooperate with chromosome genes to play a more extensive role, and regulate tumor proliferation, infiltration, metastasis and other malignant biological behaviors. [19] Figure 7.…”