Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs

Talross, Gaëlle J.S.; Deryusheva, Svetlana; Gall, Joseph G.

doi:10.1073/pnas.2114156118

Cited by 18 publications

(13 citation statements)

References 77 publications

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“…Furthermore, the presence of dyskerin in the cytoplasm was also confirmed by immunofluorescence microscopy. This finding is also in line with what has been recently reported for a sub-class of H/ACA snoRNA-bearing transcripts encoded as stable lariats that can be found in the cytoplasm associated with ectopically expressed snoRNA binding proteins such as dyskerin and GAR1 as we observed [42]. Although dyskerin is well-known to be localized in the nucleus, a previous study identified a cytoplasmic isoform of this protein characterized by a lower molecular weight [43].…”

Section: Discussionsupporting

confidence: 93%

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence

et al. 2022

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Background Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells. Results We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3′ snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs’ guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation. Conclusions Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.

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Section: Discussionsupporting

confidence: 93%

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence

et al. 2022

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“…S2, S3). Besides, scMTD identified some novel molecular function terms related to the differentiation function [ 33 – 35 ]. Furthermore, we presented the expression distributions of the marker genes participating in each stage of differentiation in the raw data and scMTD imputed data, respectively.…”

Section: Resultsmentioning

confidence: 99%

scMTD: a statistical multidimensional imputation method for single-cell RNA-seq data leveraging transcriptome dynamic information

Sheng

Zhou

et al. 2022

Cell Biosci

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Background Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to capture transcriptomes at single-cell resolution. However, dropout events distort the gene expression levels and underlying biological signals, misleading the downstream analysis of scRNA-seq data. Results We develop a statistical model-based multidimensional imputation algorithm, scMTD, that identifies local cell neighbors and specific gene co-expression networks based on the pseudo-time of cells, leveraging information on cell-level, gene-level, and transcriptome dynamic to recover scRNA-seq data. Compared with the state-of-the-art imputation methods through several real-data-based analytical experiments, scMTD effectively recovers biological signals of transcriptomes and consistently outperforms the other algorithms in improving FISH validation, trajectory inference, differential expression analysis, clustering analysis, and identification of cell types. Conclusions scMTD maintains the gene expression characteristics, enhances the clustering of cell subpopulations, assists the study of gene expression dynamics, contributes to the discovery of rare cell types, and applies to both UMI-based and non-UMI-based data. Overall, scMTD’s reliability, applicability, and scalability make it a promising imputation approach for scRNA-seq data.

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“…In addition, longer RNase R resistant stable intronic lariat bearing U85 scaRNA is observed in the nucleus (Figure S11 g). Another example of an RNase R resistant, stable intronic lariat bearing snoRNA in the oocyte nucleus is for the HSPA8 intron-encoded SNORD14 (Figure S11 f), previously described in chicken DF1 cells (Talross et al 2021). Such stable intronic lariats bearing snoRNA do not function as guide RNAs for rRNA and snRNA modification in contrast to mature snoRNA (Talross et al 2021).…”

Section: Chicken Oocyte Small Rnas Reflect Differential Cytoplasmic A...mentioning

confidence: 86%

The first chicken oocyte nucleus whole transcriptomic profile defines the spectrum of maternal mRNA and non-coding RNA genes transcribed by the lampbrush chromosomes

Krasikova,

Kulikova,

Schelkunov

et al. 2024

Preprint

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Lampbrush chromosomes, with their unusually high rate of nascent RNA synthesis, provide a valuable model for studying the mechanisms of global transcriptome up-regulation. Here, we aimed to establish a full set of sequences transcribed on the lateral loops of chicken lampbrush chromosomes. For the first time, a whole-genomic profile of transcription along the entire length of all lampbrush chromosomes in the chicken karyotype including sex chromosomes and dot chromosomes was obtained. For that, we performed RNA-seq of oocyte nuclear and cytoplasmic total RNA, poly(A) RNA and small RNA libraries and aligned expressed RNA sequences against the chicken genome. This led to the identification of a full spectrum of maternal RNAs that accumulate in the nucleus and cytoplasm of chicken oocytes at the lampbrush chromosome stage, are then transferred to the zygote and can be used during the early stages of embryogenesis, including transcripts of protein-coding genes, long non-coding RNAs and small housekeeping non-coding RNAs. We also present the first high-throughput transcriptome characterisation of miRNAs and piRNAs in chicken oocytes at the lampbrush chromosome stage. Major targets of predicted piRNAs include CR1 and LTR containing retrotransposable elements. Transcription of tandem repeat arrays including 41bp higher-order repeats as well as unique centromere sequences was demonstrated by alignment against the whole telomere-to-telomere chromosome assemblies. We show that transcription of telomere-derived RNAs, including telomeric repeat-containing RNA (TERRA) and subtelomeric repeat-containing RNA, is initiated at adjacent LTR elements. With nuclear RNA-seq, we obtained information about a wider set of transcripts, including long non-coding RNAs retained in the nucleus and stable intronic sequence RNAs (sisRNAs). We identified 5’ UTR sisRNAs that may potentially support host gene transcription both during oogenesis and after activation of the embryonic genome. For a number of protein-coding genes, we visualised nascent transcripts and demonstrated their co-transcriptional splicing on the lateral loops of lampbrush chromosomes by RNA-FISH. The nuclear RNA-seq profile predicted the chromomere-loop organisation of the genomic regions. During oocyte maturation, transcriptional unit boundaries were maintained, while transcriptional output tended to decrease. We conclude that cytoplasmic and nuclear transcripts emerge from nascent transcripts on the lateral loops of lampbrush chromosomes. Most of gene transcripts are initiated at promoters, normally spliced, terminated and polyadenylated. The set of genes transcribed on the lampbrush chromosomes is required for basic cellular processes, is characterised by a broad expression pattern and is similar to sets of genes expressed in other hypertranscriptional systems. We conclude that hypertranscription on the lateral loops of giant lampbrush chromosomes is the main mechanism for synthesising large amounts of transferred to the embryo maternal RNA for thousands of genes.

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Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs

Cited by 18 publications

References 77 publications

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence

scMTD: a statistical multidimensional imputation method for single-cell RNA-seq data leveraging transcriptome dynamic information

The first chicken oocyte nucleus whole transcriptomic profile defines the spectrum of maternal mRNA and non-coding RNA genes transcribed by the lampbrush chromosomes

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