A novel function for Sam68: Enhancement of HIV-1 RNA 3′ end processing

McLaren, Meredith; Asai, Kengo; Cochrane, Alan

doi:10.1261/rna.5263904

Cited by 42 publications

(38 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another poly(A)-binding protein, the KH-domain protein Sam68, which was shown in this and previous studies to enhance CTE function at the cytoplasmic level (Coyle et al 2003), has been reported to stimulate mRNA 39 processing, resulting in increased gene expression (McLaren et al 2004). Like Nab2, the function of Sam68 is regulated by mitogen-activated protein (MAP) kinases as well as other kinases (Matter et al 2002;Coyle et al 2003).…”

Section: Discussionmentioning

confidence: 62%

The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway

Coyle¹,

Bor²,

Rekosh³

et al. 2011

RNA

View full text Add to dashboard Cite

Post-transcriptional regulation of mRNA includes restriction mechanisms to prevent export and expression of mRNAs that are incompletely spliced. Here we present evidence that the mammalian protein Tpr is involved in this restriction. To study the role of Tpr in export of mRNA with retained introns, we used reporters in which the mRNA was exported either via the Nxf1/Nxt1 pathway using a CTE or via the Crm1 pathway using Rev/RRE. Our data show that even modest knockdown of Tpr using RNAi leads to a significant increase in export and translation from the mRNA containing the CTE. In contrast, Tpr perturbation has no effect on export of mRNA containing the RRE, either in the absence or presence of Rev. Also, no effects were observed on export of a completely spliced mRNA. Taken together, our results indicate that Tpr plays an important role in quality control of mRNA trafficked on the Nxf1 pathway.

show abstract

Section: Discussionmentioning

confidence: 62%

The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway

Coyle¹,

Bor²,

Rekosh³

et al. 2011

RNA

View full text Add to dashboard Cite

show abstract

“…Since the simultaneous activities of these proteins are necessary for maximal stimulation of v5 inclusion, it is possible that recruitment of SRm160 and Sam68 to v5 pre-mRNA is cooperative. Another indication that Sam68 and SRm160 might have common activity are the recent reports that both factors can stimulate the 3Ј-end processing of some pre-mRNAs (24,25,27).…”

Section: Discussionmentioning

confidence: 99%

Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell Invasion

Sharp

2006

Molecular and Cellular Biology

176

140

View full text Add to dashboard Cite

The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CD44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.CD44 is a transmembrane glycoprotein that mediates the response of cells to their cellular microenvironment. CD44 is expressed in most tissues, where its gene products function in lymphocyte homing, adhesion, migration, and regulation of cell growth (for review, see reference 35). This variety of roles results from multiple CD44 isoforms produced by alternative splicing (3). The CD44 gene is composed of 10 constitutively spliced exons and 10 variable exons, residing between constitutive exons 5 and 6.Interestingly, the peptides encoded by these variable exons are located in the extracellular domain of the protein. Some of these alternative spliced variants interact with growth factors and render cells responsive to extracellular stimuli (2,17,33,(37)(38)(39)43). The CD44 splice variant containing variable exon 6 (v6) can form a complex with the extracellular hepatocyte growth factor (HGF) and its tyrosine kinase receptor Met (33). Formation of this CD44 v6-HGF-Met complex stimulates the activation of Met through autophosphorylation and further activates Met-dependent Ras signaling, probably through the association of ERM (ezrin-radixin-moesin) proteins to the cytoplasmic tail of CD44 (33). The net result is that the CD44 v6-HGF-Met complex activates Ras signaling and promotes cell proliferation. Interestingly, Ras activation also stimulates transcription of CD44 and promotes inclusion of its variable exons (14,19). This constitutes a CD44-mediated positive feedback loop in the activation of Ras signaling if a factor such as HGF is present. Alternatively, the tumor suppressor protein merlin can also bind to the cytoplasmic tail of CD44. Binding of merlin to CD44 disrupts the interaction between ERM and CD44 and therefore inhibits Ras activation (29). As a result, Ras-dependent CD44 alternative splicing is inhibited, the positive feedback loop is disrupted, and cell growth diminishes. Consistent with the above observations, the majority of CD44 expressed in resting lymphocytes is in the constitutively spliced form (standard form), whereas the v...

show abstract

“…Effects of WT1(+KTS) at multiple levels would not be surprising, since many recent studies have highlighted links between different steps in RNA processing (for a recent review, see Huang and Steitz 2005). In addition, Sam68, which also functions to promote translation of CTE-containing RNA (Coyle et al 2003), has been reported to also effect alternative splicing, RNA stability, and polyadenylation (Matter et al 2002;McLaren et al 2004). …”

Section: Discussionmentioning

confidence: 99%

The Wilms’ tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron

Bor¹,

Swartz²,

Morrison³

et al. 2006

Genes Dev.

View full text Add to dashboard Cite

The Wilms' tumor 1 (WT1) gene plays an important role in mammalian urogenital development, and dysregulation of this gene is observed in many human cancers. Alternative splicing of WT1 RNA leads to the expression of two major protein isoforms, WT1(+KTS) and WT1(−KTS). Whereas WT1(−KTS) acts as a transcriptional regulator, no clear function has been ascribed to WT1(+KTS), despite the fact that this protein is crucial for normal development. Here we show that WT1(+KTS) functions to enhance expression from RNA possessing a retained intron and containing either a cellular or viral constitutive transport element (CTE). WT1(+KTS) expression increases the levels of unspliced RNA containing a CTE and specifically promotes the association of this RNA with polyribosomes. These studies provide further support for links between different steps in RNA metabolism and for the existence of post-transcriptional operons.

show abstract

A novel function for Sam68: Enhancement of HIV-1 RNA 3′ end processing

Cited by 42 publications

References 75 publications

The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway

The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway

Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell Invasion

The Wilms’ tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron

Contact Info

Product

Resources

About