Rps19 is an essential protein that is required for the biogenesis of the small ribosomal subunit. In yeast, Rps19 is encoded by duplicated genes, RPS19A and RPS19B, which differ from one another by a single amino acid. Disruption of both RPS19 genes is lethal. Disruption of either of the yeast RPS19 genes causes a reduction in growth rate and affects the production of 40 S ribosomal subunits. Rps19 is required for clevage at site A2 within ITS1 and for the maturation of the 3'-end of the 18S rRNA. In addition, Rps19 is necessary for recruitment of the non-ribosomal factors Enp1p, Tsr1p, Rio2p, normally found associated with pre-40 S particles (3).

Rps19 protein belongs to a family of ribosomal proteins restricted to eukaryotes and archaea without a homolog in the eubacterial ribosomes. The yeast Rps19 proteins have over 50% sequence identity with the human S19 (RPS19) protein with blocks of near complete identity. Haploinsufficiency and other S19 mutations in humans have been associated with Diamond-Blackfan Anemia (DBA), which is characterized by severe hypoplastic anemia that generally presents early in infancy and may be accompanied by craniofacial abnormalities, growth failure, predisposition to cancer, and other congenital abnormalities (3, 6, 7).

About yeast ribosomes...

Ribosomes are highly conserved large ribonucleoprotein (RNP) particles, consisting in yeast of a large 60S subunit and a small 40S subunit, that perform protein synthesis. Yeast ribosomes contain one copy each of four ribosomal RNAs (5S, 5.8S, 18S, and 25S; produced in two separate transcripts encoded within the rDNA repeat present as hundreds of copies on Chromosome 12) and 78 different ribosomal proteins (r-proteins), which are encoded by 137 different genes scattered about the genome, 59 of which are duplicated (8). The 60S subunit contains 42 proteins and three RNA molecules: 25S RNA of 3392 nt, hydrogen bonded to the 5.8S RNA of 158 nt and associated with the 5S RNA of 121 nt. The 40S subunit has a single 18S RNA of 1798 nt and 32 proteins (9). All yeast ribosomal proteins have a mammalian homolog (10).

In a rapidly growing yeast cell, 60% of total transcription is devoted to ribosomal RNA, and 50% of RNA polymerase II transcription and 90% of mRNA splicing are devoted to the production of mRNAs for r-proteins. Coordinate regulation of the rRNA genes and 137 r-protein genes is affected by nutritional cues and a number of signal transduction pathways that can abruptly induce or silence the ribosomal genes, whose transcripts have naturally short lifetimes, leading to major implications for the expression of other genes as well (11, 12, 13). The expression of some r-protein genes is influenced by Abf1p (14), and most are directly induced by binding of Rap1p to their promoters, which excludes nucleosomes and recruits Fhl1p and Ifh1p to drive transcription (15).

Ribosome assembly is a complex process, with different steps occurring in different parts of the cell. Ribosomal protein genes are transcribed in the nucleus, and the mRNA is transported to the cytoplasm for translation. The newly synthesized r-proteins then enter the nucleus and associate in the nucleolus with the two rRNA transcripts, one of which is methylated and pseudouridylated (view sites of modifications), and then cleaved into three individual rRNAs (18S, 5.8S, and 25S) as part of the assembly process (8). Separate ribosomal subunits are then transported from the nucleolus to the cytoplasm where they assemble into mature ribosomes before functioning in translation (16, 17). Blockage of subunit assembly, such as due to inhibition of rRNA synthesis or processing, results in degradation of newly synthesized r-proteins (18, 17). (For more information on the early steps of rRNA processing and small ribosomal subunit assembly, see the summary paragraph for the U3 snoRNA, encoded by snR17A and snR17B.)

Last updated: 2007-02-15