The story of rRNA expansion segments: Finding functionality amidst diversity

Hariharan, Nivedita; Ghosh, Sumana; Palakodeti, Dasaradhi

doi:10.1002/wrna.1732

Cited by 11 publications

(18 citation statements)

References 157 publications

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“…Eukaryotic rRNAs display several large rRNA expansion segments with largely unexplored function. The accretion of these expansion segments bears the major contribution to the increase in rRNA length and ribosome size from yeast to vertebrates (Table 1 ) (Hariharan et al , 2022 ). Furthermore, eukaryotic ribosomes contain additional RPs, and most RPs of the conserved core harbor extensions and insertions (Spahn et al , 2001 ; Armache et al , 2010 ; Ben‐Shem et al , 2011 ; Klinge et al , 2011 ; Rabl et al , 2011 ; Melnikov et al , 2012 ; Khatter et al , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Ribosome biogenesis factors—from names to functions

et al. 2023

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The assembly of ribosomal subunits is a highly orchestrated process that involves a huge cohort of accessory factors. Most eukaryotic ribosome biogenesis factors were first identified by genetic screens and proteomic approaches of pre‐ribosomal particles in Saccharomyces cerevisiae. Later, research on human ribosome synthesis not only demonstrated that the requirement for many of these factors is conserved in evolution, but also revealed the involvement of additional players, reflecting a more complex assembly pathway in mammalian cells. Yet, it remained a challenge for the field to assign a function to many of the identified factors and to reveal their molecular mode of action. Over the past decade, structural, biochemical, and cellular studies have largely filled this gap in knowledge and led to a detailed understanding of the molecular role that many of the players have during the stepwise process of ribosome maturation. Such detailed knowledge of the function of ribosome biogenesis factors will be key to further understand and better treat diseases linked to disturbed ribosome assembly, including ribosomopathies, as well as different types of cancer.

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Section: Introductionmentioning

confidence: 99%

Ribosome biogenesis factors—from names to functions

et al. 2023

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“…Experimental manipulation of rRNA of eukaryotic ribosomes in vivo is problematic, complicating the determination of functions ( 76 ). Nevertheless, expansion segment ES7 is associated with multiple functions, many of which have been recently highlighted for fungal and protist ribosomes (Group 1).…”

Section: Discussionmentioning

confidence: 99%

rRNA expansion segment 7 in eukaryotes: from Signature Fold to tentacles

Biesiada

Williams

et al. 2022

Nucleic Acids Research

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The ribosomal core is universally conserved across the tree of life. However, eukaryotic ribosomes contain diverse rRNA expansion segments (ESs) on their surfaces. Sites of ES insertions are predicted from sites of insertion of micro-ESs in archaea. Expansion segment 7 (ES7) is one of the most diverse regions of the ribosome, emanating from a short stem loop and ranging to over 750 nucleotides in mammals. We present secondary and full-atom 3D structures of ES7 from species spanning eukaryotic diversity. Our results are based on experimental 3D structures, the accretion model of ribosomal evolution, phylogenetic relationships, multiple sequence alignments, RNA folding algorithms and 3D modeling by RNAComposer. ES7 contains a distinct motif, the ‘ES7 Signature Fold’, which is generally invariant in 2D topology and 3D structure in all eukaryotic ribosomes. We establish a model in which ES7 developed over evolution through a series of elementary and recursive growth events. The data are sufficient to support an atomic-level accretion path for rRNA growth. The non-monophyletic distribution of some ES7 features across the phylogeny suggests acquisition via convergent processes. And finally, illustrating the power of our approach, we constructed the 2D and 3D structure of the entire LSU rRNA of Mus musculus.

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“…ESs still remain under-explored, even though they were discovered nearly four decades back. They may potentially have roles in diverse cellular processes such as ribosome biogenesis, post-transcriptional gene regulation and RNA metabolism (107). Therefore we think it is imperative to expand the repertoire of techniques required to probe the function of all ESs, especially because of the potential they hold in expanding the regulatory landscape of ribosomes.…”

Section: Discussionmentioning

confidence: 99%

“…Since rRNA is distributed as tandem repeats across five chromosomes in the human genome, proving our hypothesis using knock-out experiments is a challenge at present. Given their proposed and established roles in ribosome biogenesis and translation (68), an expansion of the repertoire of experimental techniques is quite important to further our understanding of these enigmatic rRNA segments. The details of these proteins are provided in Supplementary Table S4-I.…”

Section: Discussionmentioning

confidence: 99%

Expansion Segment ES30L enriched in birds and mammals can potentially regulate protein synthesis

Hariharan

Ghosh

Nallan

et al. 2022

Preprint

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Ribosomes, the molecular machines that are central to protein synthesis, have gradually been gaining prominence for their potential regulatory role in translation. Eukaryotic cytosolic ribosomes are typically larger than the bacterial ones, partly due to multi-nucleotide insertions at specific conserved positions in the ribosomal RNAs (rRNAs). Such insertions called expansion segments (ESs) are present primarily on the ribosomal surface, with their role in translation and its regulation remaining under-explored. One such ES in the ribosomal large subunit (LSU) is ES30L, which is observed mostly in mammals and birds among eukaryotes. In this study, we show that ES30L possesses complementarity to many protein-coding transcripts in humans and that the complementarity is enriched around the start codon, indicating a possible role in translation regulation. Further, our in silico analysis analyses and in vitro pull-down assays show that ES30L may bind to secondary structures in the 5′ UTR of several transcripts and RNA binding proteins (RBPs) that are essential for translation. Thus, we have identified a potential regulatory role for ES30L in translation.

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The story of rRNA expansion segments: Finding functionality amidst diversity

Cited by 11 publications

References 157 publications

Ribosome biogenesis factors—from names to functions

Ribosome biogenesis factors—from names to functions

rRNA expansion segment 7 in eukaryotes: from Signature Fold to tentacles

Expansion Segment ES30L enriched in birds and mammals can potentially regulate protein synthesis

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