mRNA stability in the nucleus

Liu, Han; Luo, Meihui; Wen, Jikai

doi:10.1631/jzus.b1400088

Cited by 29 publications

(19 citation statements)

References 91 publications

(94 reference statements)

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“…Specifically, we monitored the amount of LacZ or LacZ-4ESE transcripts in the nucleus that contained the intact PAS (i.e., uncleaved RNAs) using primers bracketing the cleavage site (Figure 2B, in red). To detect cleavage status, RNAs were isolated from nuclei in which PAS cleavage occurs (Liu et al, 2014). To confirm fraction quality, we monitored U6 snRNA and tRNA lys as nuclear and cytoplasmic markers, respectively, by semi-qRT-PCR (Figure S3A).…”

Section: Resultsmentioning

confidence: 99%

Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs

2019

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SUMMARY The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements of the 3′-end core cleavage complex involved in cleavage and polyadenylation (CPA), including CPSF3, the enzyme responsible for cleavage, as well as its co-factors CPSF1, CPSF2, CPSF4, Symplekin, WDR33, and FIP1L1. Using multiple strategies, we demonstrate that eIF4E stimulates 3′-end cleavage of selected RNAs. eIF4E physically interacts with CPSF3, CPSF1, and uncleaved target RNA, suggesting it acts directly and indirectly on the pathway. Through these effects, eIF4E can generate better substrates for its mRNA export and translation activities. Thus, we identified an unanticipated function for eIF4E in 3′-end processing of specific target RNAs, and this function could potentially affect the expression of a broad range of oncoproteins.

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Section: Resultsmentioning

confidence: 99%

Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs

2019

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“…8c). This reduced level of pre-mRNA might be due to splicing coupled transcription defect 42 or due to reduced stability of pre-mRNA owing to intron retention (splicing defect) 43 . Importantly, the relative ratio of pre-mRNA/mRNA was significantly higher with SF3B1 knockdown in both the Ishikawa and AN3CA cells, indicating that the reduced splicing efficiency in the absence of SF3B1 lead to an accumulation of pre-mature KSR2 RNA.…”

Section: Ksr2 Contributes To Sf3b1-dependent Proliferation In Endometmentioning

confidence: 99%

Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation

Popli¹,

Richters

Chadchan³

et al. 2020

Cell Death Dis

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Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the United States. Here, in an attempt to identify new prognostic and therapeutic targets, we focused on a new area for this cancer—alternative mRNA splicing—and investigated whether splicing factor, SF3B1, plays an important role in endometrial cancer pathogenesis. Using a tissue microarray, we found that human endometrial tumors expressed more SF3B1 protein than non-cancerous tissues. Furthermore, SF3B1 knockdown reduced in vitro proliferation, migration, and invasion of the endometrial cancer cell lines Ishikawa and AN3CA. Similarly, the SF3B1 inhibitor, Pladienolide-B (PLAD-B), reduced the Ishikawa and AN3CA cell proliferation and invasion in vitro. Moreover, PLAD-B reduced tumor growth in an orthotopic endometrial cancer mouse model. Using RNA-Seq approach, we identified ~2000 differentially expressed genes (DEGs) with SF3B1 knockdown in endometrial cancer cells. Additionally, alternative splicing (AS) events analysis revealed that SF3B1 depletion led to alteration in multiple categories of AS events including alternative exon skipping (ES), transcript start site usage (TSS), and transcript termination site (TTS) usage. Subsequently, bioinformatics analysis showed KSR2 as a potential candidate for SF3B1-mediated functions in endometrial cancer. Specifically, loss of SF3B1 led to decrease in KSR2 expression, owing to reduced maturation of KSR2 pre-mRNA to a mature RNA. Importantly, we found rescuing the KSR2 expression with SF3B1 knockdown partially restored the cell growth of endometrial cancer cells. Taken together, our data suggest that SF3B1 plays a crucial oncogenic role in the tumorigenesis of endometrial cancer and hence may support the development of SF3B1 inhibitors to treat this disease.

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“…Historically, mRNA degradation is only thought to occur once at least a round of translation has taken place. Liu H. et al (2014) provide an updated review of the many RNA degradation pathways taking place in the nucleus. Degrading nascent RNA transcripts in the nucleus has been viewed as a quality control mechanism to quickly get rid of undesired RNAs before they are exported to cytoplasm and waste the effort of ribosomes in translating wrong proteins.…”

Section: In This Issuementioning

confidence: 99%

Transcription: the epicenter of gene expression

Guo

2014

J. Zhejiang Univ. Sci. B

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mRNA stability in the nucleus

Cited by 29 publications

References 91 publications

Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs

Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs

Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation

Transcription: the epicenter of gene expression

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