<scp>RNA</scp> structures in alternative splicing and back‐splicing

Xu, Bingbing; Meng, Yijun; Jin, Yongfeng

doi:10.1002/wrna.1626

Cited by 48 publications

(38 citation statements)

References 329 publications

(474 reference statements)

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“…In contrast, biased splicing seems not to be economical for neurite selfavoidance, because highly biased splicing heavily limits access to the full diversity from a pool of Dscam1 isoforms (Forbes et al, 2011;Hattori et al, 2009). Although recent studies suggested that biased isoform expression may be combinatorially regulated by the strength of base pairing between the docking site and selector sequence, the strength of the splice sites, and RNAbinding proteins (Anastassiou et al, 2006;Graveley, 2005;Hong et al, 2020;Ivanov and Pervouchine, 2018;May et al, 2011;Olson et al, 2007;Smith, 2005;Wang et al, 2012;Xu et al, 2019Xu et al, , 2020Yang et al, 2011;Yue et al, 2016b), the physiological significance of the highly specific bias in isoform expression remains entirely unclear.…”

Section: Introductionmentioning

confidence: 99%

Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring

et al. 2021

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Drosophila melanogaster Down syndrome cell adhesion molecule (Dscam1) can generate 38,016 different isoforms through largely stochastic, yet highly biased, alternative splicing. These isoforms are required for nervous functions. However, the functional significance of splicing bias remains unknown. Here, we provide evidence that Dscam1 splicing bias is required for mushroom body (MB) axonal wiring. We generate mutant flies with normal overall protein levels and an identical number but global changes in exon 4 and 9 isoform bias (DscamD4D À/À and DscamD9D À/À ), respectively. In contrast to DscamD4D À/À , DscamD9D À/À exhibits remarkable MB defects, suggesting a variable domain-specific requirement for isoform bias. Importantly, changes in isoform bias cause axonal defects but do not influence the self-avoidance of axonal branches. We conclude that, in contrast to the isoform number that provides the molecular basis for neurite self-avoidance, isoform bias may play a role in MB axonal wiring by influencing non-repulsive signaling.

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Section: Introductionmentioning

confidence: 99%

Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring

et al. 2021

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“…It is also possible that Anti-N1 could trigger structural rearrangements in pre-mRNA. The role of an RNA structure in pre-mRNA splicing regulation is a growing area of interest [40,[108][109][110][111], and an ASO-based approach has been employed to abrogate structural elements critical for splicing control [39,112]. Off-target sites of Anti-N1 are expected to be randomly distributed throughout pre-mRNAs with their high prevalence in introns due to their (introns') large size.…”

Section: Discussionmentioning

confidence: 99%

High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome

Ottesen

Luo

Singh

et al. 2021

IJMS

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Intronic splicing silencer N1 (ISS-N1) located within Survival Motor Neuron 2 (SMN2) intron 7 is the target of a therapeutic antisense oligonucleotide (ASO), nusinersen (Spinraza), which is currently being used for the treatment of spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. The discovery of ISS-N1 as a promising therapeutic target was enabled in part by Anti-N1, a 20-mer ASO that restored SMN2 exon 7 inclusion by annealing to ISS-N1. Here, we analyzed the transcriptome of SMA patient cells treated with 100 nM of Anti-N1 for 30 h. Such concentrations are routinely used to demonstrate the efficacy of an ASO. While 100 nM of Anti-N1 substantially stimulated SMN2 exon 7 inclusion, it also caused massive perturbations in the transcriptome and triggered widespread aberrant splicing, affecting expression of essential genes associated with multiple cellular processes such as transcription, splicing, translation, cell signaling, cell cycle, macromolecular trafficking, cytoskeletal dynamics, and innate immunity. We validated our findings with quantitative and semiquantitative PCR of 39 candidate genes associated with diverse pathways. We also showed a substantial reduction in off-target effects with shorter ISS-N1-targeting ASOs. Our findings are significant for implementing better ASO design and dosing regimens of ASO-based drugs.

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“…Alternative splicing (AS), an important regulatory mechanism of biological process, can generate more than one transcripts including mRNA, and lncRNA [24,43] in eukaryotes by using different splice sites. There were ve fundamental groups categorized from AS events, including intron retention (IR), exon skipping (ES), alternative donor (AD), alternative acceptor (AA) and mutually exclusive exons (MX) [44].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Landscape of Pathogen-responsive Lncrnas Reveals OS_LNC1812-Induced Disease Resistance by Abscisic Acid Pathway in Rice

Cao

Gan

Cao

et al. 2021

Preprint

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Background: Long non-coding RNAs (lncRNAs) produced by the plant genome are essential regulators in diverse biological processes. Despite increasing knowledge of lncRNAs in plant development, little is known about responding to plant disease, especially in rice. Results: In this study, we investigated a comprehensive disease-responding lncRNA profiles in rice defence against Rice black-streaked dwarf virus (RBSDV) and Rice stripe virus (RSV) for the first time. Analysis of RNA sequencing of rice leaves infected with the two pathogens identified total 1,925 lncRNAs, in which 724 lncRNA were derived from alternative splicing (AS) events and the largest number of lncRNAs produced by intron retention (IR) of AS events. We calculated the regulatory relationship between transcription factors, lncRNAs, and mRNAs by constructing gene regulatory network and found that a lncRNA, OS_LNC1812 regulated by Os01t0730700-01 encoding transcription factor WRKY14 may target abscisic acid (ABA) responsive element binding factor ABF (Os01t0867300-01) involved in ABA signaling pathway during pathogens infection. We subsequently found that highly expression of OS_LNC1812, WRKY14, and ABF after ABA treatment. Conclusions: Our results reveal the common lncRNAs profiles respond to RBSDV and RSV in rice and provide novel potential modulation of lncRNAs in ABA pathway in the regulation of plant disease resistance.

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RNA structures in alternative splicing and back‐splicing

Cited by 48 publications

References 329 publications

Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring

Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring

High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome

Transcriptional Landscape of Pathogen-responsive Lncrnas Reveals OS_LNC1812-Induced Disease Resistance by Abscisic Acid Pathway in Rice

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