Regulation of translation by site-specific ribosomal RNA methylation

Jansson, Martin; Häfner, Sophia; Altinel, Kübra; Tehler, Disa; Krogh, Nicolai; Jakobsen, Emil; Andersen, Jens V.; Andersen, Kasper Langebjerg; Schoof, Erwin M.; Ménard, Patrice; Nielsen, Henrik; Lund, Anders H.

doi:10.1038/s41594-021-00669-4

Cited by 58 publications

(55 citation statements)

References 71 publications

(75 reference statements)

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“…For instance, 2′‐O‐methylation level on rRNA is regulated by MYC, which can ultimately impact translation and facilitates tumor progression. [ 129 ] Likewise, MYC can reduce the abundance of m 6 A through transcriptional activation of the m 6 A demethylase ALKBH5, [ 130 ] and also impacts m 5 C level and cell cycle progression by upregulating NSUN2. [ 131 ] It is likely that this type of regulation by a common factor is meant to achieve a coordinate cellular response for gene expression.…”

Section: Discussionmentioning

confidence: 99%

Functional interplay within the epitranscriptome: Reality or fiction?

2021

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RNA modifications have recently emerged as an important regulatory layer of gene expression. The most prevalent and reversible modification on messenger RNA (mRNA), N6‐methyladenosine, regulates most steps of RNA metabolism and its dysregulation has been associated with numerous diseases. Other modifications such as 5‐methylcytosine and N1‐methyladenosine have also been detected on mRNA but their abundance is lower and still debated. Adenosine to inosine RNA editing is widespread on coding and non‐coding RNA and can alter mRNA decoding as well as protect against autoimmune diseases. 2′‐O‐methylation of the ribose and pseudouridine are widespread on ribosomal and transfer RNA and contribute to proper RNA folding and stability. While the understanding of the individual role of RNA modifications has now reached an unprecedented stage, still little is known about their interplay in the control of gene expression. In this review we discuss the examples where such interplay has been observed and speculate that with the progress of mapping technologies more of those will rapidly accumulate.

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Section: Discussionmentioning

confidence: 99%

Functional interplay within the epitranscriptome: Reality or fiction?

2021

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“…Emerging evidence suggests snoRNA's involvement in metabolism, diabetes, cancer, and heart development (20,21,23,34). Specifically, dysregulation of SNORA47, SNORA74A, and SNORNA19 was previously described to be differentially expressed in different cancers (35)(36)(37).…”

Section: Discussionmentioning

confidence: 98%

Spaceflight-Associated Changes of snoRNAs in Peripheral Blood Mononuclear Cells and Plasma Exosomes—A Pilot Study

Kumar

Rajan

Bisserier

et al. 2022

Front. Cardiovasc. Med.

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During spaceflight, astronauts are exposed to various physiological and psychological stressors that have been associated with adverse health effects. Therefore, there is an unmet need to develop novel diagnostic tools to predict early alterations in astronauts’ health. Small nucleolar RNA (snoRNA) is a type of short non-coding RNA (60–300 nucleotides) known to guide 2′-O-methylation (Nm) or pseudouridine (ψ) of ribosomal RNA (rRNA), small nuclear RNA (snRNA), or messenger RNA (mRNA). Emerging evidence suggests that dysregulated snoRNAs may be key players in regulating fundamental cellular mechanisms and in the pathogenesis of cancer, heart, and neurological disease. Therefore, we sought to determine whether the spaceflight-induced snoRNA changes in astronaut’s peripheral blood (PB) plasma extracellular vesicles (PB-EV) and peripheral blood mononuclear cells (PBMCs). Using unbiased small RNA sequencing (sRNAseq), we evaluated changes in PB-EV snoRNA content isolated from astronauts (n = 5/group) who underwent median 12-day long Shuttle missions between 1998 and 2001. Using stringent cutoff (fold change > 2 or log2-fold change >1, FDR < 0.05), we detected 21 down-and 9—up-regulated snoRNAs in PB-EVs 3 days after return (R + 3) compared to 10 days before launch (L-10). qPCR validation revealed that SNORA74A was significantly down-regulated at R + 3 compared to L-10. We next determined snoRNA expression levels in astronauts’ PBMCs at R + 3 and L-10 (n = 6/group). qPCR analysis further confirmed a significant increase in SNORA19 and SNORA47 in astronauts’ PBMCs at R + 3 compared to L-10. Notably, many downregulated snoRNA-guided rRNA modifications, including four Nms and five ψs. Our findings revealed that spaceflight induced changes in PB-EV and PBMCs snoRNA expression, thus suggesting snoRNAs may serve as potential novel biomarkers for monitoring astronauts’ health.

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“…In addition, the same Nm residue Gm1628 also maintains electrostatic interactions with the universally conserved ribosomal protein uL23. In a recent study, the function of the snoRNA guiding Cm174 on the small subunit rRNA of the human ribosome was shown to regulate the translation of certain mRNAs by affecting the elongation rates of the ribosome (Jansson et al ., 2021). Similarly, a previous study demonstrated the role of Nm in the translation of mRNAs containing the element IRES using a human cell line inhibited by rRNA methyltransferase (Erales et al ., 2017).…”

Section: ′‐O‐methylation In Plantsmentioning

confidence: 99%

The plant epitranscriptome: revisiting pseudouridine and 2′‐O‐methyl RNA modifications

Ramakrishnan

Rajan

Mullasseri

et al. 2022

Plant Biotechnology Journal

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There is growing evidence that post-transcriptional RNA modifications are highly dynamic and can be used to improve crop production. Although more than 172 unique types of RNA modifications have been identified throughout the kingdom of life, we are yet to leverage upon the understanding to optimize RNA modifications in crops to improve productivity. The contributions of internal mRNA modifications such as N6-methyladenosine (m 6 A) and 5methylcytosine (m 5 C) methylations to embryonic development, root development, leaf morphogenesis, flowering, fruit ripening and stress response are sufficiently known, but the roles of the two most abundant RNA modifications, pseudouridine (Ψ) and 2 0 -O-methylation (Nm), in the cell remain unclear due to insufficient advances in high-throughput technologies in plant development. Therefore, in this review, we discuss the latest methods and insights gained in mapping internal Ψ and Nm and their unique properties in plants and other organisms. In addition, we discuss the limitations that remain in high-throughput technologies for qualitative and quantitative mapping of these RNA modifications and highlight future challenges in regulating the plant epitranscriptome.

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Regulation of translation by site-specific ribosomal RNA methylation

Cited by 58 publications

References 71 publications

Functional interplay within the epitranscriptome: Reality or fiction?

Functional interplay within the epitranscriptome: Reality or fiction?

Spaceflight-Associated Changes of snoRNAs in Peripheral Blood Mononuclear Cells and Plasma Exosomes—A Pilot Study

The plant epitranscriptome: revisiting pseudouridine and 2′‐O‐methyl RNA modifications

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