Analysis of two human pre-ribosomal factors, bystin and hTsr1, highlights differences in evolution of ribosome biogenesis between yeast and mammals

Abstract

Recent studies reveal that maturation of the 40S ribosomal subunit precursors in mammals includes an additional step during processing of the internal transcribed spacer 1 (ITS1), when compared with yeast Saccharomyces cerevisiae, even though the protein content of the pre-40S particle appears to be the same. Here, we examine by depletion with siRNA treatment the function of human orthologs of two essential yeast pre-ribosomal factors, hEnp1/bystin and hTsr1. Like their yeast orthologs, bystin is required for efficient cleavage of the ITS1 and further processing of this domain within the pre-40S particles, whereas hTsr1 is necessary for the final maturation steps. However, bystin depletion leads to accumulation of an unusual 18S rRNA precursor, revealing a new step in ITS1 processing that potentially involves an exonuclease. In addition, pre-40S particles lacking hTsr1 are partially retained in the nucleus, whereas depletion of Tsr1p in yeast results in strong cytoplasmic accumulation of pre-40S particles. These data indicate that ITS1 processing in human cells may be more complex than currently envisioned and that coordination between maturation and nuclear export of pre-40S particles has evolved differently in yeast and mammalian cells.

hUTP24 is essential for processing of the human rRNA precursor at site A1, but not at site A0

“…[9][10][11] Moreover, in some cases the functions of homologous proteins involved in ribosome synthesis in both species are not equivalent. [12][13][14] Furthermore, alternative pre-rRNA processing pathways are utilized in parallel in both model organisms. 7,8,15 In humans, the usage of these pathways may be highly dependent on the cell type and physiological state.…”

“…7,21 Others have argued that processing at site 2 in human cells is independent of 5 0 -ETS processing, which makes it more similar to the yeast site A 3 . 12 On the other hand, processing at site 2 in human pre-rRNA is not affected by depletion of RNase MRP subunits, while RNase MRP is responsible for A 3 cleavage in yeast. 16,22,23 The 30S pre-rRNA undergoes further endoribonucleolytic processing at 2 sites within the 5 0 -ETS, which are roughly Figure 1.…”

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

“…1 In yeast, ≈200 assembly factors and several small nucleolar RNAs have been shown to participate to these processes. In higher eukaryotes, though the core components have been conserved, differences were reported [2][3][4][5] suggesting that ribosome biogenesis has become more complex with evolution.…”

Qu’en est-il de la biogenèse des ribosomes chez l’homme ?

“…Le précurseur 21S subit une maturation séquentielle médiée par l'exosome. On peut détecter un intermédiaire (21S-C) lors de la mutation de certains facteurs d'assemblage, notamment des composants de l'exosome [5, 16,17]. Le 21S-C est coupé au site E, donnant le 18S-E, qui est alors clivé au site 3 pour générer l'ARNr mature 18S, constituant de la petite sous-unité.…”

“…Dans certaines conditions, le clivage au niveau de l'ITS1 se produit au site E plutôt qu'au site 2 [17,18], générant alors le pré-ARNr 18S-E et un précurseur appelé 36S ( Figure 2C Certains facteurs d'assemblage servent d'adaptateurs pour recruter les exportines et ont ainsi un rôle dans le contrôle de qualité. Dans le cas des précurseurs de la grande sous-unité, c'est la protéine NMD3 qui recrute l'exportine CRM1 (chromosome region maintenance 1; also referred to as exportin1 or Xpo1) [24], et, pour les pré-40S, ce sont les facteurs d'assemblage RIOK2 (RIO kinase 2) et TSR1 qui seraient requis pour lier CRM1 [16,25]. L'interaction entre CRM1 et les sousunités ribosomiques va permettre leur passage au travers des pores nucléaires, par le biais de RAN-GTP [24].…”