Alternative splicing modulates chromatin interactome and phase separation of the RIF1 C-terminal domain DOI Creative Commons

Adenine Si-Hui Koo,

Weiyan Jia, Sang Hwa Kim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

ABSTRACT RIF1 (RAP1 interacting factor) fulfills diverse roles in DNA double-strand break repair, replication, and nuclear organization. is expressed as two splice variants, RIF1-Long (RIF1-L) RIF1-Short (RIF1-S), from the alternative splicing (AS) of Exon 32 (Ex32) which encodes a 26 aa Ser/Lys-rich cassette peptide C-terminal domain (CTD). Here we demonstrate that Ex32 inclusion was repressed by damage oncogenesis but peaked at G 2 /M phase cell cycle. splice-in catalyzed positive regulators including SRSF1, bound to directly, negative such PTBP1 SRSF3. Isoform proteomics revealed enhanced association RIF1-L with MDC1, whose recruitment IR-induced foci strengthened RIF1-L. RIF1-S also exhibited unique separation chromatin-binding characteristics were regulated CDK1-dependent CTD phosphorylation. These combined findings suggest AS affects multiple aspects function genome protection Graphical Abstract HIGHLIGHTS dynamically cycle signaling. isoform switch associated primary cancers. SRSF1 acts directly on promote expression. S/K expanded chromatin interactomes stabilized separation.

Language: Английский

Comprehensive analysis of splicing factor SRs-related gene characteristics: predicting osteosarcoma prognosis and immune regulation status DOI Creative Commons

Changhai Long,

Biao Ma,

Kai Li

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 2, 2024

Objective To investigate the impact of SRs-related genes on overall survival and prognosis osteosarcoma patients through bulk single-cell RNA-seq transcriptome analysis. Methods In this study, we constructed a model based serine/arginine-rich splicing factors (SRs) predicted patients. By analyzing RNA sequencing data applying AUCell enrichment analysis, revealed oncogenic pathways SRs in immune cells. Additionally, described regulatory role SRSF7 pan-cancer. Results Lasso regression analysis identified 6 key genes, prediction was established. The upregulation these that promote tumor cell proliferation by regulating related signaling help cells evade host surveillance. grouping using AUCell, found significant differences T expression between high low-risk groups. results indicated activity is closely to function, particularly responses promoting evasion. Furthermore, regulates apoptosis. Conclusion play critical osteosarcoma. are evasion genes. gene influencing occurrence development

Language: Английский

Citations

0
YB1 and its role in osteosarcoma: a review DOI Creative Commons
Fan Wu, Dapeng Li

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 21, 2024

YB1 (Y box binding protein 1), a multifunctional capable of to DNA/RNA, is present in most cells and acts as splicing factor. It involved numerous cellular processes such transcription, translation, DNA repair, significantly affecting cell proliferation, differentiation, apoptosis. Abnormal expression this closely linked the formation various malignancies (osteosarcoma, nasopharyngeal carcinoma, breast cancer, etc.). This review examines multifaceted functions its critical role osteosarcoma progression, providing new perspectives for potential therapeutic strategies.

Language: Английский

Citations

0
Alternative splicing modulates chromatin interactome and phase separation of the RIF1 C-terminal domain DOI Creative Commons

Adenine Si-Hui Koo,

Weiyan Jia, Sang Hwa Kim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

ABSTRACT RIF1 (RAP1 interacting factor) fulfills diverse roles in DNA double-strand break repair, replication, and nuclear organization. is expressed as two splice variants, RIF1-Long (RIF1-L) RIF1-Short (RIF1-S), from the alternative splicing (AS) of Exon 32 (Ex32) which encodes a 26 aa Ser/Lys-rich cassette peptide C-terminal domain (CTD). Here we demonstrate that Ex32 inclusion was repressed by damage oncogenesis but peaked at G 2 /M phase cell cycle. splice-in catalyzed positive regulators including SRSF1, bound to directly, negative such PTBP1 SRSF3. Isoform proteomics revealed enhanced association RIF1-L with MDC1, whose recruitment IR-induced foci strengthened RIF1-L. RIF1-S also exhibited unique separation chromatin-binding characteristics were regulated CDK1-dependent CTD phosphorylation. These combined findings suggest AS affects multiple aspects function genome protection Graphical Abstract HIGHLIGHTS dynamically cycle signaling. isoform switch associated primary cancers. SRSF1 acts directly on promote expression. S/K expanded chromatin interactomes stabilized separation.

Language: Английский

Citations

0