A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Wu, Han; Sun, Shuying; Tu, Kang; Gao, Yuan; Xie, Bin; Krainer, Adrian R.; Zhu, Jun

doi:10.1016/j.molcel.2010.02.021

Cited by 175 publications

(160 citation statements)

References 52 publications

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“…For example, miR-7 transcription is directly induced by HoxD10 (Reddy et al, 2008) or c-Myc (Chou et al, 2010). Splicing factor SF2/ASF binds the pri-miR-7 to enhance its cleavage by Drosha (Wu et al, 2010). Accordingly, it is conceivable that macrophage-derived molecule(s) directly downregulate miR-7 expression or indirectly suppress miR-7 expression through modulation of these regulation systems.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells

Kong

Piao

Yamashita³

et al. 2011

Oncogene

102

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Inflammation has an important role in cancer development through various mechanisms. It has been shown that dysregulation of microRNAs (miRNAs) that function as oncogenes or tumor suppressors contributes to tumorigenesis. However, the relationship between inflammation and cancer-related miRNA expression in tumorigenesis has not yet been fully understood. Using K19-C2mE and Gan mouse models that develop gastritis and gastritis-associated tumors, respectively, we found that 21 miRNAs were upregulated, and that 29 miRNAs were downregulated in gastric tumors in an inflammation-dependent manner. Among these miRNAs, the expression of miR-7, a possible tumor suppressor, significantly decreased in both gastritis and gastric tumors. Moreover, the expression of miR-7 in human gastric cancer was inversely correlated with the levels of interleukin-1b and tumor necrosis factor-a, suggesting that miR-7 downregulation is related to the severity of inflammatory responses. In the normal mouse stomach, miR-7 expression was at a basal level in undifferentiated gastric epithelial cells, and was induced during differentiation. Moreover, transfection of a miR-7 precursor into gastric cancer cells suppressed cell proliferation and soft agar colony formation. These results suggest that suppression of miR-7 expression is important for maintaining the undifferentiated status of gastric epithelial cells, and thus contributes to gastric tumorigenesis. Although epigenetic changes were not found in the CpG islands around miR-7-1 of gastritis and gastric tumor cells, we found that activated macrophage-derived small molecule(s) (o3 kDa) are responsible for miR-7 repression in gastric cancer cells. Furthermore, the miR-7 expression level significantly decreased in the inflamed gastric mucosa of Helicobacter-infected mice, whereas it increased in the stomach of germfree K19-C2mE and Gan mice wherein inflammatory responses were suppressed.Taken together, these results indicate that downregulation of tumor suppressor miR-7 is a novel mechanism by which the inflammatory response promotes gastric tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells

Kong

Piao

Yamashita³

et al. 2011

Oncogene

102

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“…This appears to occur in part due to the activation by SRSF1 of mTORC1 through an unknown mechanism (Karni et al 2008). Like hnRNP A1, SFSR1 has been shown to have a splicing-independent role in promoting the maturation of several miRNAs, some of which are themselves up-regulated in cancer (Wu et al 2010). …”

Section: Srsf1mentioning

confidence: 99%

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

David

Manley²

2010

Genes Dev.

727

667

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Alternative splicing of mRNA precursors is a nearly ubiquitous and extremely flexible point of gene control in humans. It provides cells with the opportunity to create protein isoforms of differing, even opposing, functions from a single gene. Cancer cells often take advantage of this flexibility to produce proteins that promote growth and survival. Many of the isoforms produced in this manner are developmentally regulated and are preferentially re-expressed in tumors. Emerging insights into this process indicate that pathways that are frequently deregulated in cancer often play important roles in promoting aberrant splicing, which in turn contributes to all aspects of tumor biology.

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“…Given that SRSF1 auto-regulation is greatly mediated by its 3 0 UTR and that this region is a putative target for several miRNAs (29), the Zhu laboratory tested the hypothesized that SRSF1 could increase the expression of one or more miRNAs, which in turn repress translation of its own mRNA (20).…”

Section: Sr Protein-dependent Regulation Of Mirna Processingmentioning

confidence: 99%

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

et al. 2012

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SummarySerine/arginine-rich (SR) proteins are among the most studied splicing regulators. They constitute a family of evolutionarily conserved proteins that, apart from their initially identified and deeply studied role in splicing regulation, have been implicated in genome stability, chromatin binding, transcription elongation, mRNA stability, mRNA export and mRNA translation. Remarkably, this list of SR protein activities seems far from complete, as unexpected functions keep being unraveled. An intriguing aspect that awaits further investigation is how the multiple tasks of SR proteins are concertedly regulated within mammalian cells. In this article, we first discuss recent findings regarding the regulation of SR protein expression, activity and accessibility. We dive into recent studies describing SR protein auto-regulatory feedback loops involving different molecular mechanisms such as unproductive splicing, microRNA-mediated regulation and translational repression. In addition, we take into account another step of regulation of SR proteins, presenting new findings about a variety of post-translational modifications by proteomics approaches and how some of these modifications can regulate SR protein sub-cellular localization or stability. Towards the end, we focus in two recently revealed functions of SR proteins beyond mRNA biogenesis and metabolism, the regulation of micro-RNA processing and the regulation of small ubiquitin-like modifier (SUMO) conjugation.

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A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Cited by 175 publications

References 52 publications

Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells

Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

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