SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing

Floro, Jess; Dai, Anqi; Metzger, Abigail; Mora-Martin, Alexandra; Ganem, Neil J.; Cifuentes, Daniel; Wu, Chenwei; Dalal, Jasbir S.; Lyons, Shawn M.; Labadorf, Adam; Flynn, Rachel Litman

doi:10.1093/nar/gkab647

Cited by 11 publications

(11 citation statements)

References 80 publications

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“…To provide an example of how differential IR can bias a correct differential expression analysis of TEs, the genomic distribution of upregulated TEs was investigated in an alternative dataset characterized by a strong differential IR between two groups of samples [ 37 ]. The dataset is composed by RNA-seq data from HeLa cells treated with siRNA targeting the SDE2 gene.…”

Section: Resultsmentioning

confidence: 99%

“…SDE2 encodes for an RNA-binding protein involved, among others, in AS process. SDE2 silencing has previously resulted in global changes in AS with an increase in IR [ 37 ]. Differential IR analysis of this dataset revealed 9148 introns with increased IR in SDE2 knock-down samples ( Figure 4 G).…”

Section: Resultsmentioning

confidence: 99%

“…This dataset represents a model to test whether the validated dysregulation of TEs can be correctly identified in RNA-seq data where differential IR is not abundant. The latter is composed by RNA-seq data from SDE2 knock-down HeLa cells [ 37 ]. Data are declared as polyA RNA; however, the kit used to generate the sequencing library suggests that the RNA has to be considered as total RNA with ribosomal depletion.…”

Section: Methodsmentioning

confidence: 99%

“…SDE2 is a human RNA binding protein and a trans-acting, splicing-associated factor required for efficient RNA processing. The silencing of SDE2 in human cell lines has been associated with widespread changes in alternative splicing, with increased IR being the most frequent event [ 37 ]. This dataset represents an ideal model to explore TEs measurements in presence of differential IR.…”

Section: Methodsmentioning

confidence: 99%

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Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

Gualandi

Iperi²,

Esposito³

et al. 2022

Biology

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Transposable elements (TEs), also known as “jumping genes”, are repetitive sequences with the capability of changing their location within the genome. They are key players in many different biological processes in health and disease. Therefore, a reliable quantification of their expression as transcriptional units is crucial to distinguish between their independent expression and the transcription of their sequences as part of canonical transcripts. TEs quantification faces difficulties of different types, the most important one being low reads mappability due to their repetitive nature preventing an unambiguous mapping of reads originating from their sequences. A large fraction of TEs fragments localizes within introns, which led to the hypothesis that intron retention (IR) can be an additional source of bias, potentially affecting accurate TEs quantification. IR occurs when introns, normally removed from the mature transcript by the splicing machinery, are maintained in mature transcripts. IR is a widespread mechanism affecting many different genes with cell type-specific patterns. We hypothesized that, in an RNA-seq experiment, reads derived from retained introns can introduce a bias in the detection of overlapping, independent TEs RNA expression. In this study we performed meta-analysis using public RNA-seq data from lymphoblastoid cell lines and show that IR can impact TEs quantification using established tools with default parameters. Reads mapped on intronic TEs were indeed associated to the expression of TEs and influence their correct quantification as independent transcriptional units. We confirmed these results using additional independent datasets, demonstrating that this bias does not appear in samples where IR is not present and that differential TEs expression does not impact on IR quantification. We concluded that IR causes the over-quantification of intronic TEs and differential IR might be confused with differential TEs expression. Our results should be taken into account for a correct quantification of TEs expression from RNA-seq data, especially in samples in which IR is abundant.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

Gualandi

Iperi²,

Esposito³

et al. 2022

Biology

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show abstract

“…The cryo-EM structure of the human post-catalytic spliceosome also revealed that the N-terminal region of SDE2, not the C-terminal SAP, stabilizes Cactin into the spliceosome via its interaction with CRNKL1 (47). Notably, SDE2 is shown to associate with non-coding RNAs, though whether SDE2 SAP is required for this interaction remains unexplored (46). In our hands, recombinant SDE2 fails to form a protein-RNA complex in vitro , although we do not exclude the possibility that SDE2 recognizes specific structures of rRNA or snoRNA in association with the riboprotein complex ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Extended DNA binding interface beyond the canonical SAP domain contributes to SDE2 function at DNA replication forks

Weinheimer

Paung

Rageul

et al. 2022

Preprint

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Elevated DNA replication stress causes instability of the DNA replication fork and DNA mutations, which underlies tumorigenesis. The DNA replication stress regulator SDE2 binds to TIMELESS (TIM) of the fork protection complex (FPC) and enhances its stability, thereby supporting replisome activity at DNA replication forks. Here, we structurally and functionally characterize a new conserved DNA binding motif related to SAP (SAF-A/B, Acinus, PIAS) in human SDE2 and establish its preference for single-stranded DNA (ssDNA). The nuclear magnetic resonance solution structure of SDE2SAP reveals a helix-extended loop-helix core aligned parallel to each other, consistent with known canonical SAP folds. Notably, its DNA interaction extends beyond the core SAP domain and is augmented by two lysine residues in the C-terminal tail, which is uniquely positioned adjacent to SAP and conserved in the pre-mRNA splicing factor SF3A3. Mutation in the SAP domain with extended C-terminus not only disrupts ssDNA binding but also impairs TIM localization at replication forks, thus inhibiting efficient fork progression. Together, our study establishes SDE2SAP as an essential element for SDE2 to exert its role in preserving replication fork integrity via FPC regulation and highlights the structural diversity of the DNA-protein interactions achieved by a specialized DNA binding motif.

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Enigmatic Nodal and Lefty gene repertoire discrepancy: Latent evolutionary history revealed by vertebrate‐wide phylogeny

Kuraku

2024

Developmental Dynamics

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Homology in vertebrate body plans is traditionally ascribed to the high‐level conservation of regulatory components within the genetic programs governing them, particularly during the “phylotypic stage.” However, advancements in embryology and molecular phylogeny have unveiled the dynamic nature of gene repertoires responsible for early development. Notably, the Nodal and Lefty genes, members of the transforming growth factor‐beta superfamily producing intercellular signaling molecules and crucial for left–right (L‐R) symmetry breaking, exhibit distinctive features within their gene repertoires. These features encompass among‐species gene repertoire variations resulting from gene gain and loss, as well as gene conversion. Despite their significance, these features have been largely unexplored in a phylogenetic context, but accumulating genome‐wide sequence information is allowing the scrutiny of these features. It has exposed hidden paralogy between Nodal1 and Nodal2 genes resulting from differential gene loss in amniotes. In parallel, the tandem cluster of Lefty1 and Lefty2 genes, which was thought to be confined to mammals, is observed in sharks and rays, with an unexpected phylogenetic pattern. This article provides a comprehensive review of the current understanding of the origins of these vertebrate gene repertoires and proposes a revised nomenclature based on the elucidated history of vertebrate genome evolution.

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SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing

Cited by 11 publications

References 80 publications

Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

Extended DNA binding interface beyond the canonical SAP domain contributes to SDE2 function at DNA replication forks

Enigmatic Nodal and Lefty gene repertoire discrepancy: Latent evolutionary history revealed by vertebrate‐wide phylogeny

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