scholarly journals Pan‐cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential

2020 ◽  
Vol 24 (19) ◽  
pp. 11111-11119
Author(s):  
Hao Li ◽  
Jingwei Liu ◽  
Shixuan Shen ◽  
Di Dai ◽  
Shitong Cheng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Heterogeneous Nuclear Ribonucleoproteins ◽  
Splicing Regulator ◽  
Pan Cancer

U2AF - Hypoxia-induced fas alternative splicing regulator

2021 ◽  
Vol 399 (1) ◽  
pp. 112444
Author(s):  
Laurynas Vilys ◽  
Inga Peciuliene ◽  
Egle Jakubauskiene ◽  
Ruta Zinkeviciute ◽  
Yuichi Makino ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splicing Regulator

scholarly journals Repression of Prespliceosome Complex Formation at Two Distinct Steps by Fox-1/Fox-2 Proteins

2008 ◽  
Vol 28 (17) ◽  
pp. 5507-5516 ◽  
Author(s):  
Hua-Lin Zhou ◽  
Hua Lou
Keyword(s):  
Alternative Splicing ◽  
Complex Formation ◽  
Biochemical Analysis ◽  
Expression Control ◽  
Regulatory Strategy ◽  
Gene Expression Control ◽  
Splicing Regulator ◽  
Specific Alternative ◽  
Novel Strategy ◽  
Robust Regulation

ABSTRACT Precise and robust regulation of alternative splicing provides cells with an essential means of gene expression control. However, the mechanisms that ensure the tight control of tissue-specific alternative splicing are not well understood. It has been demonstrated that robust regulation often results from the contributions of multiple factors to one particular splicing pathway. We report here a novel strategy used by a single splicing regulator that blocks the formation of two distinct prespliceosome complexes to achieve efficient regulation. Fox-1/Fox-2 proteins, potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specific splicing of the calcitonin/CGRP pre-mRNA. Using biochemical analysis, we found that Fox-1/Fox-2 proteins block prespliceosome complex formation at two distinct steps through binding to two functionally important UGCAUG elements. First, Fox-1/Fox-2 proteins bind to the intronic site to inhibit SF1-dependent E′ complex formation. Second, these proteins bind to the exonic site to block the transition of E′ complex that escaped the control of the intronic site to E complex. These studies provide evidence for the first example of regulated E′ complex formation. The two-step repression of presplicing complexes by a single regulator provides a powerful and accurate regulatory strategy.

scholarly journals Epithelial Splicing Regulator Protein 1 and Alternative Splicing in Somatotroph Adenomas

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 3331-3343 ◽  
Author(s):  
Tove Lekva ◽  
Jens Petter Berg ◽  
Robert Lyle ◽  
Ansgar Heck ◽  
Geir Ringstad ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Importance ◽  
Somatostatin Analog ◽  
Gh3 Cells ◽  
Mesenchymal Transition ◽  
Regulator Protein ◽  
Splicing Pattern ◽  
Splicing Regulator ◽  
Granulation Pattern

Somatotroph adenomas secrete supraphysiological amounts of GH, causing acromegaly. We have previously hypothesized that epithelial mesenchymal transition (EMT) may play a central role in the progression of these adenomas and that epithelial splicing regulator 1 (ESRP1) may function prominently as a master regulator of the EMT process in pituitary adenomas causing acromegaly. To further elucidate the role of ESRP1 in somatotroph adenomas and in EMT progression, we used RNA sequencing (RNAseq) to sequence somatotroph adenomas characterized by high and low ESRP1 levels. Transcripts identified by RNAseq were analyzed in 65 somatotroph adenomas and in GH-producing pituitary rat cells with a specific knockdown of Esrp1. The clinical importance of the transcripts was further investigated by correlating mRNA expression levels with clinical indices of disease activity and treatment response. Many of the transcripts and isoforms identified by RNAseq and verified by quantitative PCR were involved in vesicle transport and calcium signaling and were associated with clinical outcomes. Silencing Esrp1 in GH3 cells resulted in changes of gene expression overlapping the data observed in human somatotroph adenomas and revealed a decreased granulation pattern and attenuated GH release. We observed an alternative splicing pattern for F-box and leucine-rich repeat protein 20, depending on the ESPR1 levels and on changes in circulating IGF-I levels after somatostatin analog treatment. Our study indicates that ESRP1 in somatotroph adenomas regulates transcripts that may be essential in the EMT progression and in the response to somatostatin analog treatment.

scholarly journals hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei-zhao Peng ◽  
Ji-xi Liu ◽  
Chao-feng Li ◽  
Ren Ma ◽  
Jian-zheng Jie
Keyword(s):  
Alternative Splicing ◽  
Standard Form ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Stem Cell Marker ◽  
Start Codon ◽  
Migration And Invasion ◽  
Regulation Mechanism ◽  
Loss Of Function ◽  
Splicing Regulator

Abstract Background The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood. Methods Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated. Results The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (− 65 to − 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). Conclusion These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

scholarly journals Axonogenesis Is Coordinated by Neuron-Specific Alternative Splicing Programming and Splicing Regulator PTBP2

Neuron ◽  
2019 ◽  
Vol 101 (4) ◽  
pp. 690-706.e10 ◽  
Author(s):  
Min Zhang ◽  
Volkan Ergin ◽  
Lin Lin ◽  
Cheryl Stork ◽  
Liang Chen ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splicing Regulator ◽  
Specific Alternative

scholarly journals The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy

2010 ◽  
Vol 29 (7) ◽  
pp. 1235-1247 ◽  
Author(s):  
Simona Pedrotti ◽  
Pamela Bielli ◽  
Maria Paola Paronetto ◽  
Fabiola Ciccosanti ◽  
Gian Maria Fimia ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Splicing Silencer ◽  
Splicing Regulator

scholarly journals PSI controls tim splicing and circadian period in Drosophila

2018 ◽  
Author(s):  
Lauren Foley ◽  
Jinli Ling ◽  
Radhika Joshi ◽  
Naveh Evantal ◽  
Sebastian Kadener ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Circadian Rhythms ◽  
Translational Regulation ◽  
Transcriptional Control ◽  
Rna Binding ◽  
P Element ◽  
Peripheral Tissues ◽  
Associated Proteins ◽  
Splicing Regulator ◽  
Post Transcriptional Regulation

AbstractThe Drosophila circadian pacemaker consists of transcriptional feedback loops subjected to both post-transcriptional and post-translational regulation. While post-translational regulatory mechanisms have been studied in detail, much less is known about circadian post-transcriptional control. To have a better understanding of the role and mechanisms of circadian post-transcriptional regulation, we targeted 364 RNA binding and RNA associated proteins with RNA interference. Among the 43 genes we identified was the alternative splicing regulator P-element somatic inhibitor (PSI). PSI downregulation shortens the period of circadian rhythms both in the brain and in peripheral tissues. Interestingly, we found that PSI regulates the thermosensitive alternative splicing of timeless (tim), promoting splicing events favored at warm temperature over those increased at cold temperature. Moreover, the period of circadian behavior was insensitive to PSI downregulation when flies could produce functional TIM proteins only from a transgene that cannot form the thermosensitive splicing isoforms. Therefore, we conclude that PSI regulates the period of Drosophila circadian rhythms through its modulation of the tim splicing pattern.

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