Tudor Staphylococcal Nuclease (Tudor-SN) Participates in Small Ribonucleoprotein (snRNP) Assembly via Interacting with Symmetrically Dimethylated Sm Proteins

Gao, Xingjie; Zhao, Xiujuan; Yu, Zhu; He, Jian‐Qing; Shao, Jie; Su, Chao; Zhang, Yi; Zhang, Wei; Saarikettu, Juha; Silvennoinen, Olli; Yao, Zhi; Yang, Jie

doi:10.1074/jbc.m111.311852

Cited by 55 publications

(56 citation statements)

References 56 publications

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“…[26][27][28] In this work, we have focused our attention on SND1 (Figure 1a), a transcriptional regulator that is also implicated in mRNA processing. 36,37 First, by comparing its expression levels in PCa cells (LNCaP and PC3) with respect to cells derived from a benign prostate hyperplasia (BPH1), we found that SND1 was expressed at higher levels in PCa cells, similar to SAM68 (Figure 1c). Nucleus/cytoplasm fractionations of LNCaP and PC3 cell extracts indicated that SND1 is localized in both the nucleus and the cytoplasm (Figure 1d), consistent with its function in transcription, RNA interference and mRNA stability.…”

Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 93%

“…SND1 cooperates with SAM68 in favoring CD44 exon v5 inclusion Given the proposed role of SND1 in mRNA splicing, 36,37 we asked whether it could modulate the splicing activity of SAM68. As model system, we used CD44, for its relevance in cancer as the inclusion of its variable exons correlates with tumor development and metastasis.…”

Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 99%

“…36,37 We hypothesized that SND1 may exert its stimulatory effect on CD44 AS by promoting efficient assembly of the spliceosome within the variable region of the gene. To test this possibility, we labeled nascent pre-mRNAs by incubating the cells for 45 min with BrU after their release from the DRB block.…”

Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 99%

“…34,35 Furthermore, it interacts with the snRNPs and accelerates the kinetics of spliceosome assembly, thereby facilitating pre-mRNA splicing. 36,37 SND1 is also a component of the RNA-induced silencing complex that regulates RNAi-mediated gene silencing. 38 With regard to our study, recent evidence has suggested a positive role of SND1 in carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells

et al. 2013

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Splicing abnormalities have profound impact in human cancer. Several splicing factors, including SAM68, have pro-oncogenic functions, and their increased expression often correlates with human cancer development and progression. Herein, we have identified using mass spectrometry proteins that interact with endogenous SAM68 in prostate cancer (PCa) cells. Among other interesting proteins, we have characterized the interaction of SAM68 with SND1, a transcriptional co-activator that binds spliceosome components, thus coupling transcription and splicing. We found that both SAM68 and SND1 are upregulated in PCa cells with respect to benign prostate cells. Upregulation of SND1 exerts a synergic effect with SAM68 on exon v5 inclusion in the CD44 mRNA. The effect of SND1 on CD44 splicing required SAM68, as it was compromised after knockdown of this protein or mutation of the SAM68-binding sites in the CD44 pre-mRNA. More generally, we found that SND1 promotes the inclusion of CD44 variable exons by recruiting SAM68 and spliceosomal components on CD44 pre-mRNA. Inclusion of the variable exons in CD44 correlates with increased proliferation, motility and invasiveness of cancer cells. Strikingly, we found that knockdown of SND1, or SAM68, reduced proliferation and migration of PCa cells. Thus, our findings strongly suggest that SND1 is a novel regulator of alternative splicing that promotes PCa cell growth and survival.Oncogene advance online publication, 2 September 2013; doi:10.1038/onc.2013.360Keywords: alternative splicing; SND1; SAM68; CD44; prostate cancer INTRODUCTION Nuclear processing of pre-mRNAs requires tightly regulated steps that ultimately yield a mature and functional mRNA. Splicing is the step that insures the removal of long non-coding sequences (introns) from the pre-mRNA and the joining of the exons. This phenomenon is driven by a large macromolecular complex, the spliceosome, composed of five small nuclear ribonucleoproteins (snRNPs) and over 200 auxiliary proteins. 1 In higher eukaryotes, a large number of exons can be alternatively spliced to yield different transcripts from a single gene, thereby increasing the coding potential of the genome. 2,3 Indeed, the large majority of multi-exon human genes undergo alternative splicing (AS) to produce at least two mRNA variants. 4,5 As regulation of AS profoundly influences physiological and pathological processes, 3,6 the full comprehension of the molecular mechanisms regulating this step of pre-mRNA processing is of fundamental importance.Splicing is physically and functionally coupled to transcription. 7-10 Two models have been proposed for how transcription might affect changes in AS patterns. The 'recruitment model' suggests that the transcription apparatus physically interacts with splicing regulators, thereby affecting splicing decisions. The C-terminal domain (CTD) of the largest subunit of the RNA polymerase II (RNAPII) has a central role in this coupling process by favoring the recruitment of RNA processing factors on the nascent transcripts. 9,10 ...

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Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 93%

Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 99%

Section: Identification Of Snd1 As a Novel Sam68-interacting Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells

et al. 2013

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“…SND1 has a Tudor homology domain and five repeated staphylococcal nuclease homology domains (Callebaut and Mornon, 1997) suggested to act as interaction platforms for proteins and RNAs, respectively (Shaw et al, 2007;Li et al, 2008). SND1 has been implicated in a variety of cellular processes such as transcription (Tong et al, 1995;Dash et al, 1996;Leverson et al, 1998;Wang et al, 2010), RNA splicing Gao et al, 2012) and RNA metabolism (Gao et al, 2010). SND1 has also been reported as one of the components of the RNA-induced silencing complex (RISC), which mediates gene silencing (Caudy et al, 2003).…”

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confidence: 99%

SND1 Affects Proliferation of Hepatocellular Carcinoma Cell Line SMMC‐7721 by Regulating IGFBP3 Expression

Yin

Jing

Huang

et al. 2013

The Anatomical Record

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Staphylococcal nuclease domain containing 1 (SND1) is a ubiquitously expressed multifunctional protein involved in transcriptional regulation, RNA splicing and RNA metabolism. Ectopic expression of SND1 has been observed in various tumors including colon cancer, breast cancer, prostate cancer and hepatocellular carcinoma (HCC), indicating a positive role of SND1 in tumor initiation and progression. However, the exact role of SND1 in cancers has not been thoroughly investigated. In the present study, we investigated the role of SND1 in HCC. Immunohistochemistry analysis revealed that the expression level of SND1 was higher in HCC tissues than in adjacent nontumor tissues. Stable knockdown of SND1, performed on the HCC cell line SMMC-7721 using shRNA lentiviral expression system, led to reduced cell proliferation, clone formation and tumor formation in nude mice. The insulin-like growth factor (IGF) signaling pathway was frequently dysregulated in HCC, which could facilitate tumor progression. Screening of gene expression levels of the IGF pathway, using real-time PCR, revealed that a decrease in SND1 expression could increase the expression of IGF-binding protein 3 (IGFBP3), which can negatively regulate activation of the IGF pathway by restricting interactions between IGF and IGF receptors. Results from previous studies showed that the downregulation of IGFBP3 expression is Additional Supporting Information may be found in the online version of this article.Jie Yin and Jianmin Ding contributed equally to this work.

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MicroRNA‐127 is Downregulated by Tudor‐SN Protein and Contributes to Metastasis and Proliferation in Breast Cancer Cell Line MDA‐MB‐231

Zhao

Duan

Liu

et al. 2013

The Anatomical Record

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Tudor-SN is a multifunctional protein that is highly expressed in multiple cancers including breast cancer. Tudor-SN, as a component in RNA-induced splicing complex, was recently reported to regulate gene expression in a micro-RNA (miRNA)-dependent manner, such as let-7, miR-34a and miR-221. However, how Tudor-SN is associated with cancer development still remains largely elusive. In the present study, we explored the role of Tudor-SN in breast cancer. Stable knockdown of endogenous Tudor-SN, performed on the breast cancer cell line MDA-MB-231 by small hairpin RNA expression vectors, suppressed the in vitro migration and invasion ability of the metastatic breast cancer cell line. Interestingly, we found Tudor-SN as a miRNA regulator according to microarray analysis, and further identified that Tudor-SN negatively regulated the expression of miR-127, and consequently increased the expression of the proto-oncogene BCL6 which was a convincing target of miR-127. Moreover, overexpression of miR-127 reduced the in vitro migration and proliferation ability of breast cancer cell MDA-MB-231. Collectively, our results suggested a novel mechanism that Tudor-SN promoted metastasis and proliferation of breast cancer cells via downregulating the miR-127 expression.

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Tudor Staphylococcal Nuclease (Tudor-SN) Participates in Small Ribonucleoprotein (snRNP) Assembly via Interacting with Symmetrically Dimethylated Sm Proteins

Cited by 55 publications

References 56 publications

The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells

The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells

SND1 Affects Proliferation of Hepatocellular Carcinoma Cell Line SMMC‐7721 by Regulating IGFBP3 Expression

MicroRNA‐127 is Downregulated by Tudor‐SN Protein and Contributes to Metastasis and Proliferation in Breast Cancer Cell Line MDA‐MB‐231

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