Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits.
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.
O'Donohue
Marie-Françoise
MF
Laboratoire de Biologie Moléculaire des Eucaryotes, Université de Toulouse-UPS and Centre National de La Recherche Scientifique, F-31000 Toulouse, France.
Choesmel
Valérie
V
Faubladier
Marlène
M
Fichant
Gwennaële
G
Gleizes
Pierre-Emmanuel
PE
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D029503:Anemia, Diamond-Blackfan / Q000235:genetics / Q000378:metabolism; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D012322:RNA Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D012322:RNA Precursors; D012335:RNA, Ribosomal; D012337:RNA, Ribosomal, 18S; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins
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