The U1 antisense morpholino oligonucleotide (AMO) disrupts U1 snRNP structure to promote intronic PCPA modification of pre-mRNAs

Feng, Qiumin; Lin, Zejin; Deng, Yanhui; Yi, Ran; Yu, Ran; Xiang, Andy Peng; Ye, Congting; Yao, Chengguo

doi:10.1016/j.jbc.2023.104854

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…1 E ). These results are in line with previous research conducted by our team and others ( 1 – 3 , 7 , 15 , 16 ). In contrast, the analysis revealed that 12,166 up-regulated intronic PASs were identified in U4 AMO-transfected samples, distributed among 5,227 genes ( Fig.…”

Section: Resultssupporting

confidence: 94%

“…We previously demonstrated that U1 AMO disrupts the structure of U1 snRNP, thereby promoting intronic PCPA of pre-mRNAs ( 7 ). To further explore the potential role of splicing in the U1 telescripting mechanism, we employed an AMO targeting U4 snRNA, a crucial core component of the spliceosome ( 8 , 9 ) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the association of the U1 telescripting mechanism with transcription regulation ( 3 , 7 ), we hypothesized that U4 AMO may also disrupt transcription. To investigate this hypothesis, ChIP-seq analysis was conducted in HeLa cells using an antibody specific to the RNAPII CTD (C-terminal domain).…”

Section: Resultsmentioning

confidence: 99%

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U4 snRNP inhibits premature cleavage and polyadenylation of pre-mRNAs

Feng,

Zhao,

Lin

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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The essential role of U4 snRNP in pre-messenger RNA (mRNA) splicing has been well established. In this study, we utilized an antisense morpholino oligonucleotide (AMO) specifically targeting U4 snRNA to achieve functional knockdown of U4 snRNP in HeLa cells. Our results showed that this knockdown resulted in global intronic premature cleavage and polyadenylation (PCPA) events, comparable to the effects observed with U1 AMO treatment, as demonstrated by mRNA 3′-seq analysis. Furthermore, our study suggested that this may be a common phenomenon in both human and mouse cell lines. Additionally, we showed that U4 AMO treatment disrupted transcription elongation, as evidenced by chromatin immunoprecipitation sequencing (ChIP-seq) analysis for RNAPII. Collectively, our results identified a unique role for U4 snRNP in the inhibition of PCPA and indicated a model wherein splicing intrinsically inhibits intronic cleavage and polyadenylation in the context of cotranscriptional mRNA processing.

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Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

U4 snRNP inhibits premature cleavage and polyadenylation of pre-mRNAs

Feng,

Zhao,

Lin

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape

Boddu,

Gupta,

Roy

et al. 2024

Molecular Cell

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InPACT: a computational method for accurate characterization of intronic polyadenylation from RNA sequencing data

Liu,

Chen,

et al. 2024

Nat Commun

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Alternative polyadenylation can occur in introns, termed intronic polyadenylation (IPA), has been implicated in diverse biological processes and diseases, as it can produce noncoding transcripts or transcripts with truncated coding regions. However, a reliable method is required to accurately characterize IPA. Here, we propose a computational method called InPACT, which allows for the precise characterization of IPA from conventional RNA-seq data. InPACT successfully identifies numerous previously unannotated IPA transcripts in human cells, many of which are translated, as evidenced by ribosome profiling data. We have demonstrated that InPACT outperforms other methods in terms of IPA identification and quantification. Moreover, InPACT applied to monocyte activation reveals temporally coordinated IPA events. Further application on single-cell RNA-seq data of human fetal bone marrow reveals the expression of several IPA isoforms in a context-specific manner. Therefore, InPACT represents a powerful tool for the accurate characterization of IPA from RNA-seq data.

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The U1 antisense morpholino oligonucleotide (AMO) disrupts U1 snRNP structure to promote intronic PCPA modification of pre-mRNAs

Cited by 3 publications

References 42 publications

U4 snRNP inhibits premature cleavage and polyadenylation of pre-mRNAs

U4 snRNP inhibits premature cleavage and polyadenylation of pre-mRNAs

Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape

InPACT: a computational method for accurate characterization of intronic polyadenylation from RNA sequencing data

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