Abstract
Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism. In eukaryotes, they are produced from a long primary transcript through an intricate sequence of processing steps that include RNA cleavage and folding and nucleotide modification. The mechanisms underlying this process in human cells have long been investigated, but technological advances have accelerated their study in the past decade. In addition, the association of congenital diseases to defects in ribosome synthesis has highlighted the central place of ribosomal RNA maturation in cell physiology regulation and broadened the interest in these mechanisms. Here, we give an overview of the current knowledge of pre-ribosomal RNA processing in human cells in light of recent progress and discuss how dysfunction of this pathway may contribute to the physiopathology of congenital diseases.
Highlights
Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism
Pre-rRNAs were initially described in mammalian cells, but the intricate molecular mechanisms underlying their maturation initially described in mammalian cells, but the intricate molecular mechanisms underlying their were largely deciphered in yeast Saccharomyces cerevisiae, which became the gold standard for these maturation were largely deciphered in yeast Saccharomyces cerevisiae, which became the gold standard studies [21,22]
This and revealed a higher complexity of these mechanisms when compared to yeast [23,24,25,26,27]. This renewed renewed interest in human pre-rRNA maturation has been fueled by the discovery of a growing interest in human pre-rRNA maturation has been fueled by the discovery of a growing class of class of inheritable diseases, called ribosomopathies, that are characterized by defects in ribosome inheritable diseases, called ribosomopathies, that are characterized by defects in ribosome production production or function [28,29]
Summary
Endonucleolytic cleavage of the ITS2 requires prior cleavage of the ITS1 Because of these coexisting pathways, the ratio between the rRNA precursors may vary among cell types and are drastically modified in some pathological contexts [41,42] or during viral infection [43]. These modified pre-rRNA patterns indicate changes in the relative kinetics of the processing steps and may reflect defects in ribosome biogenesis. Further work is needed to demonstrate whether changing the order of cleavages may impact ribosome maturation per se and lead to structural variability in ribosomes, for example by modifying the kinetics, and thereby the pattern, of rRNA post-transcriptional modifications [44]
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