On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective

Andrzejewska, Angelika; Zawadzka, Małgorzata; Pachulska-Wieczorek, Katarzyna

doi:10.3390/ijms21186770

Cited by 25 publications

(27 citation statements)

References 111 publications

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“…In addition, as almost half of the ‐20°C upregulated transcripts were also enriched in P‐bodies (Figure 8d ), it is possible that AU‐rich transcripts enjoy a better protection from degradation at ‐20°C by e.g., some P‐body or EV‐components than the GC‐rich transcripts. Likewise, factors known to influence RNA degradation such as mRNA structure (Akiyama et al., 2016 ; Andrzejewska et al., 2020 ), poly‐A tail length contributing to protective structures at 3′ end (Akiyama et al., 2016 ), and preference of nucleases for certain sequences (Courel et al., 2019 ) should be considered. Gene ontology analysis revealed that the downregulated genes in the ‐20°C group were associated with biological functions of glucose and lipid metabolism and with the compartment of EV (Figure 9 ).…”

Section: Discussionmentioning

confidence: 99%

Urinary extracellular vesicles: Assessment of pre‐analytical variables and development of a quality control with focus on transcriptomic biomarker research

Barreiro

Dwivedi

Valkonen

et al. 2021

J of Extracellular Vesicle

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Urinary extracellular vesicles (uEV) are a topical source of non-invasive biomarkers for health and diseases of the urogenital system. However, several challenges have become evident in the standardization of uEV pipelines from collection of urine to biomarker analysis. Here, we studied the effect of pre-analytical variables and developed means of quality control for uEV isolates to be used in transcriptomic biomarker research. We included urine samples from healthy controls and individuals with type 1 or type 2 diabetes and normo-, micro-or macroalbuminuria and isolated uEV byThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionmentioning

confidence: 99%

Urinary extracellular vesicles: Assessment of pre‐analytical variables and development of a quality control with focus on transcriptomic biomarker research

Barreiro

Dwivedi

Valkonen

et al. 2021

J of Extracellular Vesicle

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“…However, the in vivo structure of Ty1 gRNA or other LTR-retrotransposon transcripts has not been determined. Moreover, as compared to Escherichia coli , plant or mammalian cells, much less is known about the folding of mRNA in yeast ( 34 ). The first transcriptome-wide measurement of yeast mRNA structure was performed in vitro using an enzymatic PARS method (Parallel Analysis of RNA Structure), which suggested that mRNA transcripts with similar biological functions or cellular localization have common structural features ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

In vivostructure of the Ty1 retrotransposon RNA genome

Andrzejewska

Zawadzka

Gumna

et al. 2021

Nucleic Acids Research

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Long terminal repeat (LTR)-retrotransposons constitute a significant part of eukaryotic genomes and influence their function and evolution. Like other RNA viruses, LTR-retrotransposons efficiently utilize their RNA genome to interact with host cell machinery during replication. Here, we provide the first genome-wide RNA secondary structure model for a LTR-retrotransposon in living cells. Using SHAPE probing, we explore the secondary structure of the yeast Ty1 retrotransposon RNA genome in its native in vivo state and under defined in vitro conditions. Comparative analyses reveal the strong impact of the cellular environment on folding of Ty1 RNA. In vivo, Ty1 genome RNA is significantly less structured and more dynamic but retains specific well-structured regions harboring functional cis-acting sequences. Ribosomes participate in the unfolding and remodeling of Ty1 RNA, and inhibition of translation initiation stabilizes Ty1 RNA structure. Together, our findings support the dual role of Ty1 genomic RNA as a template for protein synthesis and reverse transcription. This study also contributes to understanding how a complex multifunctional RNA genome folds in vivo, and strengthens the need for studying RNA structure in its natural cellular context.

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“…Third, we note that the ultimate goal of studying SVRs is to understand the functional roles of RNA structure, which often involves cross-examination of other data sources, including motif analysis of RBPs, multi-omics datasets, etc. Incorporation of these multi-source data may help to accurately annotate SVRs 11 .…”

Section: Discussionmentioning

confidence: 99%

“…There are various mature high-throughput SP platforms, such as SHAPE-Seq 7,8 , DMS-Seq 9 , and icSHAPE 10 . These platforms offer flexible options for tackling different biological problems, and have achieved success in uncovering pervasive links between RNA structure and RNA function 11 .…”

Section: Introductionmentioning

confidence: 99%

Differential Analysis of RNA Structure Probing Experiments at Nucleotide Resolution: Uncovering Regulatory Functions of RNA Structure

Zhang

et al. 2021

Preprint

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RNAs perform their function by forming specific structures, which can change across cellular conditions. Structure probing experiments combined with next generation sequencing technology have enabled transcriptome-wide analysis of RNA secondary structure in various cellular conditions. Differential analysis of structure probing data in different conditions can reveal the RNA structurally variable regions (SVRs), which is important for understanding RNA functions. Here, we propose DiffScan, a computational framework for normalization and differential analysis of structure probing data in high resolution. DiffScan preprocesses structure probing datasets to remove systematic bias, and then scans the transcripts to identify SVRs and adaptively determines their lengths and locations. The proposed approach is compatible with most structure probing platforms (e.g., icSHAPE, DMS-seq). When evaluated with simulated and benchmark datasets, DiffScan identifies structurally variable regions at nucleotide resolution, with substantial improvement in accuracy compared with existing SVR detection methods. Moreover, the improvement is robust when tested in multiple structure probing platforms. Application of DiffScan in a dataset of multi-subcellular RNA structurome identified multiple regions that form different structures in nucleus and cytoplasm, linking RNA structural variation to regulation of mRNAs encoding mitochondria-associated proteins. This work provides an effective tool for differential analysis of RNA secondary structure, reinforcing the power of structure probing experiments in deciphering the dynamic RNA structurome.

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On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective

Cited by 25 publications

References 111 publications

Urinary extracellular vesicles: Assessment of pre‐analytical variables and development of a quality control with focus on transcriptomic biomarker research

Urinary extracellular vesicles: Assessment of pre‐analytical variables and development of a quality control with focus on transcriptomic biomarker research

In vivostructure of the Ty1 retrotransposon RNA genome

Differential Analysis of RNA Structure Probing Experiments at Nucleotide Resolution: Uncovering Regulatory Functions of RNA Structure

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