Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits

Marie-Françoise O'Donohue; Valérie Choesmel; Marlène Faubladier; Gwennaële Fichant; Pierre-Emmanuel Gleizes

doi:10.1083/jcb.201005117

Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits

J Cell Biol. 2010 Sep 6;190(5):853-66. doi: 10.1083/jcb.201005117.

Authors

Marie-Françoise O'Donohue¹, Valérie Choesmel, Marlène Faubladier, Gwennaële Fichant, Pierre-Emmanuel Gleizes

Affiliation

¹ Laboratoire de Biologie Moléculaire des Eucaryotes, Université de Toulouse-UPS and Centre National de La Recherche Scientifique, F-31000 Toulouse, France.

Abstract

Our knowledge of the functions of metazoan ribosomal proteins in ribosome synthesis remains fragmentary. Using siRNAs, we show that knockdown of 31 of the 32 ribosomal proteins of the human 40S subunit (ribosomal protein of the small subunit [RPS]) strongly affects pre-ribosomal RNA (rRNA) processing, which often correlates with nucleolar chromatin disorganization. 16 RPSs are strictly required for initiating processing of the sequences flanking the 18S rRNA in the pre-rRNA except at the metazoan-specific early cleavage site. The remaining 16 proteins are necessary for progression of the nuclear and cytoplasmic maturation steps and for nuclear export. Distribution of these two subsets of RPSs in the 40S subunit structure argues for a tight dependence of pre-rRNA processing initiation on the folding of both the body and the head of the forming subunit. Interestingly, the functional dichotomy of RPS proteins reported in this study is correlated with the mutation frequency of RPS genes in Diamond-Blackfan anemia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / genetics
Anemia, Diamond-Blackfan / genetics
Anemia, Diamond-Blackfan / metabolism
Cell Nucleolus / genetics
Cell Nucleolus / metabolism
Cell Nucleus / genetics
Cell Nucleus / metabolism
Chromatin / metabolism
Cytoplasm / genetics
Cytoplasm / metabolism
HeLa Cells
Humans
Mutation
RNA Precursors / analysis
RNA Precursors / genetics
RNA Precursors / metabolism
RNA, Ribosomal / chemistry
RNA, Ribosomal / genetics
RNA, Ribosomal / metabolism
RNA, Ribosomal, 18S / analysis
RNA, Ribosomal, 18S / genetics
RNA, Ribosomal, 18S / metabolism
RNA, Small Interfering / analysis
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Ribosomal Proteins / analysis
Ribosomal Proteins / genetics*
Ribosomal Proteins / metabolism*
Ribosome Subunits, Small, Eukaryotic / metabolism*
Ribosomes / chemistry
Ribosomes / genetics
Ribosomes / metabolism

Substances

Chromatin
RNA Precursors
RNA, Ribosomal
RNA, Ribosomal, 18S
RNA, Small Interfering
Ribosomal Proteins