Analysis of the effect of the presence of 7S pre-rRNA on 60S subunits on translation in S. cerevisiae

• Grant number: 23/06344-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2023
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Columbano de Oliveira
• Grantee: Bruno Roberto da Silva Queiroz
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/00901-1 - Posttranscriptional control of gene expression: pre-rRNA processing, mRNA degradation, splicing and snoRNP assembly in Saccharomyces cerevisiae, AP.TEM

Abstract

The ribosome is a complex and essential molecular machinery for all organisms, as it is responsible for translating information encoded in genomes for protein synthesis in cells. Ribosomal biogenesis is a process that involves multiple steps of processing and maturation of ribosomal RNAs and their association with proteins for the formation of 60S and 40S subunits in eukaryotes. The yeast 60S ribosomal subunit is composed of several proteins and three ribosomal RNAs, named 25S, 5.8S, and 5S. The 25S, 18S, and 5.8S ribosomal RNAs are transcribed as a long precursor RNA, called 35S, which contains the sequences of the three ribosomal RNAs interspersed and flanked by spacer sequences. Exosomal RNA is an enzymatic complex with multiple subunits, which participates in the processing of ribosomal RNAs, essential for ribosomal biogenesis. Some mutants of exosome subunits and ribosome assembly factors show failures in ribosomal RNA processing leading to defects in the ribosome. Mutants of the Nop53 protein, an important ribosomal biogenesis factor, accumulate the 7S pre-rRNA and can produce aberrant but partially functional ribosomes. In this work, we propose to analyze the effects of the presence of the 7S pre-rRNA in the 60S subunit on translation in Saccharomyces cerevisiae. Given the evolutionary conservation of the ribosomal biogenesis process and the factors involved in this pathway, the results of this study may help us to elucidate the mechanisms by which mutations in exosome subunits and in ribosome assembly factors cause human diseases related to ribosome malfunction called ribosome disorders. (AU)