Staufen1-Mediated mRNA Decay Functions in Adipogenesis

Cho, Hanna; Kim, Kyoung Mi; Han, Sisu; Choe, Joong-Seon; Park, Seung Gu; Choi, Sun Shim; Kim, Yoon Ki

doi:10.1016/j.molcel.2012.03.009

Cited by 100 publications

(143 citation statements)

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“…Which activity is observed depends on the cellular context, the identity of the bound RNA and the location of the binding site on the target RNA. Many of Staufen's previously documented activities parallel those of the EJC [7][8][9][10][11]19,20,33,[35][36][37][38] . To better understand EJC function, we recently determined the complete EJC RNA-binding landscape in HEK293 cells 24 .…”

Section: Discussionmentioning

confidence: 95%

“…Like many RNA-binding factors, the Drosophila and mammalian Staufen proteins have been implicated in multiple post-transcriptional processes including alternative splicing 13 , RNA localization 4,6,[30][31][32] , translational activation 7 and translation-dependent mRNA decay [8][9][10][11]14,20,33,34 . Which activity is observed depends on the cellular context, the identity of the bound RNA and the location of the binding site on the target RNA.…”

Section: Discussionmentioning

confidence: 99%

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Staufen1 senses overall transcript secondary structure to regulate translation

Ricci

Küçükural

Cenik

et al. 2013

Nat Struct Mol Biol

122

184

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Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3′ untranslated regions (UTRs) or in 'strongly distal' 3′ UTRs. Stau1 also interacts with actively translating ribosomes and with mRNA coding sequences (CDSs) and 3′ UTRs in proportion to their GC content and propensity to form internal secondary structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater ribosome densities, thus suggesting a general role for Stau1 in modulating translation elongation through structured CDS regions. Our results also indicate that Stau1 regulates translation of transcription-regulatory proteins.Staufen proteins are highly conserved dsRNA-binding proteins (dsRBPs) found in most bilateral animals 1 . Mammals contain two Staufen paralogs encoded by different loci. Stau1, Reprints and permissions information is available online at

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Staufen1 senses overall transcript secondary structure to regulate translation

Ricci

Küçükural

Cenik

et al. 2013

Nat Struct Mol Biol

122

184

View full text Add to dashboard Cite

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“…It is known that the N-terminal region of UPF1 interacts with several adaptors and effectors, including PNRC2, UPF2, and SMG6 (Mendell et al 2000;Cho et al 2009Cho et al , 2012Okada-Katsuhata et al 2012). In addition, our previous report revealed that down-regulation of PNRC2, but not UPF2, inhibits GMD (Cho et al 2015).…”

Section: Efficient Gmd Requires An Interaction Between Upf1 and Pnrc2mentioning

confidence: 99%

Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay

Park

et al. 2016

Genes Dev.

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Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction complexindependent manner, confirming that GMD is mechanistically distinct from nonsense-mediated mRNA decay (NMD). Efficient GMD requires PNRC2 (proline-rich nuclear receptor coregulatory protein 2) binding, helicase ability, and ATM-mediated phosphorylation of UPF1 (upstream frameshift 1). We also identify two GMD-specific factors: an RNA-binding protein, YBX1 (Y-box-binding protein 1), and an endoribonuclease, HRSP12 (heat-responsive protein 12). In particular, using HRSP12 variants, which are known to disrupt trimerization of HRSP12, we show that HRSP12 plays an essential role in the formation of a functionally active GMD complex. Moreover, we determine the hierarchical recruitment of GMD factors to target mRNAs. Finally, our genome-wide analysis shows that GMD targets a variety of transcripts, implicating roles in a wide range of cellular processes, including immune responses.

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“…Among the verified splicing targets, several SRSF10-affected splicing events have been implicated in adipogenesis, such as ACLY (13), axin1 (11,12), Upf1 (14), and lipin1 (15). Significantly, two alternatively spliced isoforms of lipin1 have been shown to display distinct functions in adipocyte differentiation (8).…”

Section: Validation Of Srsf10-affected Alternative Splicing Targetsmentioning

confidence: 99%

“…To investigate the molecular basis for this, we used a transcriptome sequencing (RNA-seq) approach to identify SRSF10-regulated splicing events in MEF cells. Several SRSF10-affected splicing events which have been implicated in adipogenesis have been identified, including axin1 (11), ACLY (12,13), Upf1 (14), and lipin1 (15).…”

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confidence: 99%

SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation

Huang

Cheng

et al. 2014

Molecular and Cellular Biology

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bDuring adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue (WAT) as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, transcriptome sequencing (RNA-seq) analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Notably, lipin1, known as an important regulator during adipogenesis, was further investigated. While lipin1␤ is mainly involved in lipogenesis, its alternatively spliced isoform lipin1␣, generated through the skipping of exon 7, is primarily required for initial adipocyte differentiation. Skipping of exon 7 is controlled by an SRSF10-regulated cis element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1␣ mRNA. 〈 series of experiments demonstrated that SRSF10 controls the production of lipin1␣ and thus promotes adipocyte differentiation. Indeed, lipin1␣ expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing.

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Staufen1-Mediated mRNA Decay Functions in Adipogenesis

Cited by 100 publications

References 37 publications

Staufen1 senses overall transcript secondary structure to regulate translation

Staufen1 senses overall transcript secondary structure to regulate translation

Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay

SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation

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