Dataset Information

Cell-specific post-transcriptional regulation of ?-synuclein gene by micro-RNAs.

ABSTRACT: ?-Synuclein is a member of the synucleins family of small proteins, which consists of three members:?, ?- and ?-synuclein. ?-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, ?-synuclein expression is strongly correlated with disease progression, and can stimulate proliferation, induce invasion and metastasis of cancer cells. ?-Synuclein transcription is regulated basically through the binding of AP-1 to specific sequences in intron 1. Here we show that ?-synuclein expression may be also regulated by micro RNAs (miRs) on post-transcriptional level. According to prediction by several methods, the 3'-untranslated region (UTR) of ?-synuclein gene contains targets for miRs. Insertion of ?-synuclein 3'-UTR downstream of the reporter luciferase (LUC) gene causes a 51% reduction of LUC activity after transfection into SKBR3 and Y79 cells, confirming the presence of efficient targets for miRs in this fragment. Expression of miR-4437 and miR-4674 for which putative targets in 3'-UTR were predicted caused a 61.2% and 60.1% reduction of endogenous ?-synuclein expression confirming their role in gene expression regulation. On the other hand, in cells overexpressing ?-synuclein no significant effect of miRs on ?-synuclein expression was found suggesting that miRs exert their regulatory effect only at low or moderate, but not at high level of ?-synuclein expression. Elevated level of ?-synuclein differentially changes the level of several miRs expression, upregulating the level of some miRs and downregulating the level of others. Three miRs upregulated as a result of ?-synuclein overexpression, i.e., miR-885-3p, miR-138 and miR-497 have putative targets in 3'-UTR of the ?-synuclein gene. Some of miRs differentially regulated by ?-synuclein may modulate signaling pathways and cancer related gene expression. This study demonstrates that miRs might provide cell-specific regulation of ?-synuclein expression and set the stage to further evaluate their role in pathophysiological processes.

SUBMITTER: Surgucheva I

PROVIDER: S-EPMC3770685 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.

Surgucheva Irina I Gunewardena Sumedha S Rao H Shanker HS Surguchov Andrei A

PloS one 20130911 9

γ-Synuclein is a member of the synucleins family of small proteins, which consists of three members:α, β- and γ-synuclein. γ-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, γ-synuclein expression is strongly correlated with disease progression, and can stimulate proliferation, induce invasion and metastasis of cancer cells. γ-Synuclein transcription is regulated basically through the binding of AP-1 to sp ...[more]

PMID: 24040069

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Project description:BackgroundTranscriptional regulation is a fundamental process in biological systems, where transcription factors (TFs) have been revealed to play crucial roles. In recent years, in addition to TFs, an increasing number of non-coding RNAs (ncRNAs) have been shown to mediate post-transcriptional processes and regulate many critical pathways in both prokaryotes and eukaryotes. On the other hand, with more and more high-throughput biological data becoming available, it is possible and imperative to quantitatively study gene regulation in a systematic and detailed manner.ResultsMost existing studies for inferring transcriptional regulatory interactions and the activity of TFs ignore the possible post-transcriptional effects of ncRNAs. In this work, we propose a novel framework to infer the activity of regulators including both TFs and ncRNAs by exploring the expression profiles of target genes and (post)transcriptional regulatory relationships. We model the integrated regulatory system by a set of biochemical reactions which lead to a log-bilinear problem. The inference process is achieved by an iterative algorithm, in which two linear programming models are efficiently solved. In contrast to available related studies, the effects of ncRNAs on transcription process are considered in this work, and thus more reasonable and accurate reconstruction can be expected. In addition, the approach is suitable for large-scale problems from the viewpoint of computation. Experiments on two synthesized data sets and a model system of Escherichia coli (E. coli) carbon source transition from glucose to acetate illustrate the effectiveness of our model and algorithm.ConclusionOur results show that incorporating the post-transcriptional regulation of ncRNAs into system model can mine the hidden effects from the regulation activity of TFs in transcription processes and thus can uncover the biological mechanisms in gene regulation in a more accurate manner. The software for the algorithm in this paper is available upon request.

Dataset Information

Cell-specific post-transcriptional regulation of ?-synuclein gene by micro-RNAs.

Publications

Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.

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