Functional characterization of Nop53/PICT1: modulation of ribosome biogenesis, the exosome activity, and effect on cell cycle

• Grant number: 15/05776-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2015
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Columbano de Oliveira
• Grantee: Felipe Franco de Melo Bagatelli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 10/51842-3 - Structural study of protein components of the exosome and some of its regulatory factors from Archaea and yeast, AP.TEM

Abstract

Ribosomes are highly conserved ribonucleic complexes responsible for the translation of messenger RNAs (mRNA), catalyzing the protein synthesis in the cytoplasm. In Eukaryotes, they are composed of two subunits, namely 40S and 60S. The first is comprised of the 18S ribosomal RNA (rRNA) and 33 ribosomal proteins, while the second is constituted by the association of 25S, 5.8S and 5S rRNA with 46 ribosomal proteins.The biogenesis of such complexes starts in the nucleolus as an extremely energy consuming, highly orchestrated process with several steps, in which approximately 200 non-ribosomal proteins and 76 non-coding RNAs take part. Despite recent progress regarding the description of new assembly factors, the discovery of rRNA processing mechanisms and the structural characterization of both subunits at different stages of maturation, it still remains to be elucidated the specific roles performed by several non-ribosomal proteins in the formation and maturation of pre-40S and pre-60S.Nop53, an essential nucleolar protein in Saccharomyces cerevisiae, was observed to affect late steps of pre-60S maturation and to interact with rRNA processing factors, such as the exosome catalytic subunit Rrp6. It was also seen to directly interact with 5.8S rRNA, which is the product of the exosome 3'-5' processing of the 7S pre-rRNA. The human Nop53 ortholog, the protein PICT1 (GTSCR2), has been described as a tumor suppressor and was also found as part of the pre-60S subunit.In spite of the advances in description of Nop53 and PICT1, their roles in the large ribosomal subunit maturation, as well as their influence on the exosome exonucleolytic activity still remain poorly understood. The major aim of this project is the functional characterization of the nucleolar protein Nop53 in S. cerevisiae, elucidating its role in the ribosome biogenesis, cell cycle regulation and the modulation of the nuclear exosome activity, evaluating the mechanisms by which it affects the levels of Rrp6 expression. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CEPEDA, LEIDY PAOLA P.; BAGATELLI, FELIPE F. M.; SANTOS, RENATA M.; SANTOS, MARLON D. M.; NOGUEIRA, FABIO C. S.; OLIVEIRA, CARLA C.. The ribosome assembly factor Nop53 controls association of the RNA exosome with pre-60S particles in yeast. Journal of Biological Chemistry, v. 294, n. 50, p. 19365+, DEC 13 2019. (15/06477-9, 15/05776-2)

BAGATELLI, FELIPE F. M.; DE LUNA VITORINO, FRANCISCA N.; DA CUNHA, JULIA P. C.; OLIVEIRA, CARLA C.. The ribosome assembly factor Nop53 has a structural role in the formation of nuclear pre-60S intermediates, affecting late maturation events. Nucleic Acids Research, v. 49, n. 12, p. 7053-7074, JUL 9 2021. (15/05776-2, 15/06477-9, 13/07467-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BAGATELLI, Felipe Franco de Melo. Characterization of the role of Nop53 in the assembly of the large ribosomal subunit in Saccharomyces cerevisiae. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.