A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity

Kawashima, Hidenori; Takano, Haruna; Sugita, Syozo; Takahara, Yuki; Sugimura, Kazunobu; Nakatani, Tatsuya

doi:10.1042/bj20020743

Cited by 91 publications

(92 citation statements)

References 27 publications

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“…As well as the generation of small RNAs generated by cleavage, there are several precedents for ncRNAs being processed from an mRNA precursor, such as mirtrons from splice junctions (Ruby et al 2007) and endogenous siRNAs from mRNA duplexes (Okamura and Lai 2008). The ability to generate a range of noncoding transcripts from a coding precursor provides an intersecting avenue between the protein-coding and noncoding transcriptomes, thereby contributing to an increased blurring of the dichotomy between coding and regulatory transcripts (Kawashima et al 2003;ChooniedassKothari et al 2004;Dinger et al 2008). …”

Section: Discussionmentioning

confidence: 99%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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The complexity of the eukaryotic transcriptome is generated by the interplay of transcription initiation, termination, alternative splicing, and other forms of post-transcriptional modification. It was recently shown that RNA transcripts may also undergo cleavage and secondary 59 capping. Here, we show that post-transcriptional cleavage of RNA contributes to the diversification of the transcriptome by generating a range of small RNAs and long coding and noncoding RNAs. Using genomewide histone modification and RNA polymerase II occupancy data, we confirm that the vast majority of intraexonic CAGE tags are derived from post-transcriptional processing. By comparing exonic CAGE tags to tissue-matched PARE data, we show that the cleavage and subsequent secondary capping is regulated in a developmental-stage-and tissue-specific manner. Furthermore, we find evidence of prevalent RNA cleavage in numerous transcriptomic data sets, including SAGE, cDNA, small RNA libraries, and deep-sequenced size-fractionated pools of RNA. These cleavage products include mRNA variants that retain the potential to be translated into shortened functional protein isoforms. We conclude that post-transcriptional RNA cleavage is a key mechanism that expands the functional repertoire and scope for regulatory control of the eukaryotic transcriptome.

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Section: Discussionmentioning

confidence: 99%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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“…These receptors in turn exert their function on downstream targets by recruiting additional transcription and epigenetic factors, including ATP-dependent chromatin remodeling complexes and histone acetyltransferases (HATs) (Gronemeyer et al 2004). Interestingly, SRA is a bifunctional transcript, with one isoform functioning as ncRNA and another as mRNA that is translated into the protein SRAP (Kawashima et al 2003;Chooniedass-Kothari et al 2004), which may in turn antagonize the function of its noncoding counterpart (Hubé et al 2011). Conversely, an example of a lncRNA corepressor can be found at the cyclin D1 (CCND1) locus, where a series of independently transcribed, variable-length lncRNAs called ncRNA CCND1 are upregulated during stress (Klein and Assoian 2008;Wang et al 2008).…”

Section: Mechanisms Of Action: Finding Pattern In Chaosmentioning

confidence: 99%

“…Like the identification of new transcripts, however, just because an RNA is translated should not automatically be taken to mean that these peptides are functional, but could instead be "translational noise." Moreover, it would be a false dichotomy to maintain that a transcript must either be coding or be noncoding-the example of SRA/SRAP demonstrates that an RNA could potentially function at multiple levels, both as a ncRNA performing a regulatory role and as an mRNA for protein synthesis (Kawashima et al 2003;Chooniedass-Kothari et al 2004).…”

Section: Translated Lncrnas: Pervasive Translation or Gene Evolution mentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

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Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

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“…While all these studies refer to SRA as a noncoding RNA, we have previously demonstrated the existence of coding SRA RNA isoforms and corresponding endogenous SRA proteins, 12 highly conserved in vertebrates and expressed in breast cancer cell lines. 13,14 To date, no data are available on the possible role of the coding SRA RNA or SRAP in breast cancer cells or on their expression in human breast tumor tissues.…”

mentioning

confidence: 99%

The steroid receptor RNA activator protein is expressed in breast tumor tissues

Chooniedass-Kothari

Hamedani

Troup

et al. 2005

Intl Journal of Cancer

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The steroid receptor RNA activator (SRA) was originally described as the first functional non-coding RNA able to specifically coactivate the activity of steroid receptors. We previously demonstrated the existence in breast cancer cell lines of new SRA isoforms that, as opposed to the first cloned SRA RNA, encode for a 236-amino acid protein, SRAP. To investigate the possible implications of the coding SRA RNA and SRAP expression on breast cancer progression, we examined by Western blot analysis 74 primary breast tumors of patients subsequently treated with tamoxifen. Patients whose primary tumors were positive for SRAP expression (n 5 24) had a significantly (Kaplan-Meier survival curve p 5 0.047) lower likelihood of dying from recurrent disease than SRAP-negative patients (n 5 50). We generated 2 cell lines, SRAP-V5-High.A and SRAP-V5-High.B, by stably overexpressing SRAP in the estrogen receptor-positive MCF-7 breast cancer cell line. Transient transfection experiments, performed using a luciferase reporter gene under the control of an estrogen-responsive element, revealed decreased sensitivity to estradiol but no additional sensitivity to tamoxifen in SRAP-overexpressing cells. Overall, our data suggest that the presence of both coding SRA RNA and its corresponding SRAP modifies the activity of estrogen receptor in breast cancer cells and that SRAP could be a new clinical marker for breast cancer. Further studies are needed to define the respective mechanisms of action and the roles of SRA RNA and protein in breast tumorigenesis and tumor progression. ' 2005 Wiley-Liss, Inc.Key words: steroid receptor coactivator; human breast tumor; steroid receptor coactivator protein Through its action on breast epithelial cells, estrogen not only controls the growth and the development of normal mammary gland but also promotes breast tumorigenesis and breast cancer progression. 1 The biological action of estrogen is mainly mediated through two ERs, a and b, which act as ligand-dependent transcription factors. 2,3 While estrogen initially plays a pivotal role in the activation of ERs, the transcriptional activation of target genes is ultimately determined by interactions between receptors and regulatory molecules known as coactivators and corepressors, which respectively stimulate or inhibit ER activity. 4 SRA differs from all previously characterized coactivators as it was originally identified as a functional non-coding RNA molecule. 5 SRA mechanisms of action have since become the focus of extensive investigation. SRA was shown to contain a core RNA sequence necessary and sufficient to mediate steroid receptor activity 6 through interactions with several proteins including the coactivator/corepressor SHARP, 7 SRC1, 5 and the AF-1-specific activator p72/p68 protein. 8 Post-transcriptional modifications of SRA have also been shown to participate in the ability of this RNA to modulate receptor activity. 9 We established that SRA RNA was differentially expressed in normal and in breast tumor tissue and suggested that SRA R...

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A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity

Cited by 91 publications

References 27 publications

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Long Noncoding RNAs: Past, Present, and Future

The steroid receptor RNA activator protein is expressed in breast tumor tissues

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