Biography
Biography: Zeina Nasr
Abstract
Protein synthesis is a highly regulated and coordinated process involving the action of ribosomes and a set of translation factors. Ribosome biogenesis occurs in the nucleolus and requires the action of 80 ribosomal proteins (RPs), 4 ribosomal RNAs (rRNAs), other associated proteins and small nucleolar RNAs. The structure of the ribosomal subunits has identified the role of RPs as RNA chaperones for ribosomal assembly, and as endo- and exonucleases essential for the maturation of rRNAs. Some play a role in the joining of 40S and 60S subunits during translation initiation. Others interact with tRNA or stabilize the ribosome by encasing the exit groove. Studies have also shown that RPs may have extraribosomal functions, ranging from DNA repair to replication, proliferation, apoptosis, and chemoresistance. Mutations in RPs in animal models and humans induced a wide variety of phenotypes suggesting a role of RPs beyond the ribosome structure. Thus far, 11 RP mutant mice have been reported exhibiting diverse phenotypes including decrease body size, defective organs, and embryonic lethality. Defects in ribosome biogenesis have been linked to many diseases collectively named ribosomopathies. These include Myelodysplatic Syndromes, due to RPS14 haploinsufficiency and Diamond Blackfan Anemia, caused by mutations in RPS19 gene. These abnormalities have shown an increase susceptibility to hematological malignancies. Indeed, RPs have been linked to tumorigenesis in several reports, suggesting a role in promoting transformation. Several RPs are overexpressed upon activation of the oncogene Myc. Some are found overexpressed in various human tumors, including prostate and colon cancer, metastatic nasopharyngeal carcinomas, metastatic melanomas and metastatic human breast cancer cells. Some RPs have also been proposed as biomarkers for various cancers, such as colorectal, gastric, prostate cancers and lymph node metastasis. These pieces of evidence suggest that RPs could be used as potential targets in cancer therapeutics.