Ribosomal RNA Pseudouridylation: Will Newly Available Methods Finally Define the Contribution of This Modification to Human Ribosome Plasticity?

Barozzi, Chiara; Zacchini, Federico; Asghar, Sidra; Montanaro, Lorenzo

doi:10.3389/fgene.2022.920987

Cited by 7 publications

(8 citation statements)

References 63 publications

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“…In fact, the current availability of Bisulfite-Induced Deletion sequencing (BID)-Seq, HydraPsiSeq and the applications of single molecule sequencing (e.g. nanopore) to pseudouridine detection will likely lead in the near future to a detailed characterization of the alterations involving this specific modification in cancer and possibly in other physiological and pathological conditions ( 23 , 33 , 34 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although the isomerization of uridine has been widely studied, little is known about the effects of dysregulation of pseudouridylation on rRNA, primarily due to technical limitations in site-specific pseudouridine detection ( 23 ). This was firstly accomplished by CMC treatment followed by alkaline hydrolysis, which selectively and irreversibly binds to pseudouridine leading to premature truncation of retrotranscription at the modified site.…”

Section: Introductionmentioning

confidence: 99%

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Alterations of ribosomal RNA pseudouridylation in human breast cancer

et al. 2023

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RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2′O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and they are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alterations of ribosomal RNA pseudouridylation in human breast cancer

et al. 2023

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“…For instance, the rRNAs of the human 80S ribosome contain 104 Ψs (modified by 66 different Box H/ACA RNPs) that were identified by mass spectrometry in TK6 cells. [1,55] Overall, rRNA pseudouridylation not only contributes to the folding and stabilization of the ribosomes, [56] but also plays a role in rRNA biogenesis and protein translation . [57] It has been reported that rRNA pseudouridylation can also affect Internal Ribosome Entry Site (IRES)-mediated translation.…”

Section: ψ and Translationmentioning

confidence: 99%

RNA‐Guided RNA Pseudouridylation and 2’‐O‐Methylation

Adachi,

Chen,

Leeder

et al. 2024

Israel Journal of Chemistry

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RNA‐guided RNA modifications, including pseudouridylation and 2′‐O‐methylation, are naturally occurring processes that introduce pseudouridines (Ψ) and 2’‐O‐methylated residues (2’‐O−Me) into various types of RNA. This modification is orchestrated by two distinct families of ribonucleoprotein complexes: Box H/ACA RNP and Box C/D RNP. Each complex comprises a unique guide (g)RNA (Box H/ACA gRNA or Box C/D gRNA) and a set of core proteins responsible for pseudouridylation and 2’‐O‐methylation, respectively. The specificity of these modifications is conferred by base‐pairing of Box H/ACA gRNA and Box C/D gRNA with their RNA substrates. Here, we discuss the mechanism and function of RNA‐guided pseudouridylation and 2’‐O‐methylation.

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“…In multicellular organisms, ribosome function is associated with development, growth and cell cycle (Barozzi et al, 2022). Eukaryotic rRNA are modified frequently, and twelve different types of rRNA modifications have been characterized in yeast (Sloan et al, 2017).…”

Section: Conserved G1177 Is the Putative Methylation Site In 18s Rrna...mentioning

confidence: 99%

Overexpression of 18S rRNA methyltransferase CrBUD23 enhances biomass and lutein content in Chlamydomonas reinhardtii

Liu

Guo²,

Zhao³

et al. 2023

Front. Bioeng. Biotechnol.

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Post-transcriptional modification of nucleic acids including transfer RNA (tRNA), ribosomal RNA (rRNA) and messenger RNA (mRNA) is vital for fine-tunning of mRNA translation. Methylation is one of the most widespread post-transcriptional modifications in both eukaryotes and prokaryotes. HsWBSCR22 and ScBUD23 encodes a 18S rRNA methyltransferase that positively regulates cell growth by mediating ribosome maturation in human and yeast, respectively. However, presence and function of 18S rRNA methyltransferase in green algae are still elusive. Here, through bioinformatic analysis, we identified CrBUD23 as the human WBSCR22 homolog in genome of the green algae model organism Chlamydonomas reinhardtii. CrBUD23 was a conserved putative 18S rRNA methyltransferase widely exited in algae, plants, insects and mammalians. Transcription of CrBUD23 was upregulated by high light and down-regulated by low light, indicating its role in photosynthesis and energy metabolism. To characterize its biological function, coding sequence of CrBUD23 fused with a green fluorescence protein (GFP) tag was derived by 35S promoter and stably integrated into Chlamydomonas genome by glass bead-mediated transformation. Compared to C. reinhardtii wild type CC-5325, transgenic strains overexpressing CrBUD23 resulted in accelerated cell growth, thereby leading to elevated biomass, dry weight and protein content. Moreover, overexpression of CrBUD23 increased content of photosynthetic pigments but not elicit the activation of antioxidative enzymes, suggesting CrBUD23 favors growth and proliferation in the trade-off with stress responses. Bioinformatic analysis revealed the G1177 was the putative methylation site in 18S rRNA of C. reinhardtii CC-849. G1177 was conserved in other Chlamydonomas isolates, indicating the conserved methyltransferase activity of BUD23 proteins. In addition, CrTrm122, the homolog of BUD23 interactor Trm112, was found involved in responses to high light as same as CrBUD23. Taken together, our study revealed that cell growth, protein content and lutein accumulation of Chlamydomonas were positively regulated by the 18S rRNA methyltransferase CrBUD23, which could serve as a promising candidate for microalgae genetic engineering.

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Ribosomal RNA Pseudouridylation: Will Newly Available Methods Finally Define the Contribution of This Modification to Human Ribosome Plasticity?

Cited by 7 publications

References 63 publications

Alterations of ribosomal RNA pseudouridylation in human breast cancer

Alterations of ribosomal RNA pseudouridylation in human breast cancer

RNA‐Guided RNA Pseudouridylation and 2’‐O‐Methylation

Overexpression of 18S rRNA methyltransferase CrBUD23 enhances biomass and lutein content in Chlamydomonas reinhardtii

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