Transcriptional mechanisms controlling miR-375 gene expression in the pancreas.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-20 DOI:10.1155/2012/891216
Tali Avnit-Sagi, Tal Vana, Michael D Walker
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引用次数: 17

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that play an important role in mediating a broad and expanding range of biological activities. miR-375 is expressed selectively in the pancreas. We have previously shown that selective expression of miR-375 in pancreatic beta cells is controlled by transcriptional mechanisms operating through a TATA box-containing promoter. Expression of miR-375 has been reported in non-beta cells within the endocrine pancreas, and indeed inactivation of miR-375 leads to perturbation in cell mass and number of both alpha and beta cells. Consistent with its expression throughout the endocrine pancreas, we now show that the promoter of the miR-375 gene shows selective activity in pancreatic endocrine alpha cells, comparable to that observed in beta cells. We previously identified a novel negative regulatory element located downstream of the miR-375 gene transcription start site. By generating luciferase reporter genes, we now show that the sequence is functional also when positioned upstream of a heterologous promoter, thus proving that the repressor effect is mediated at least in part at the level of transcription. Further characterization of the transcriptional control mechanism regulating expression of miR-375 and other pancreatic miRNAs will contribute to a better understanding of pancreas development and function.

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胰腺中调控miR-375基因表达的转录机制
MicroRNAs (miRNAs)是一类小的非编码rna,在介导广泛且不断扩大的生物活性方面发挥着重要作用。miR-375在胰腺中选择性表达。我们之前已经表明,miR-375在胰腺β细胞中的选择性表达是由转录机制控制的,该机制通过一个TATA盒启动子运作。据报道,miR-375在内分泌胰腺的非β细胞中表达,miR-375的失活确实会导致细胞质量和α细胞和β细胞数量的扰动。与其在整个内分泌胰腺中的表达一致,我们现在发现miR-375基因的启动子在胰腺内分泌α细胞中表现出选择性活性,与在β细胞中观察到的活性相当。我们之前发现了位于miR-375基因转录起始位点下游的一个新的负调控元件。通过生成荧光素酶报告基因,我们现在表明该序列在位于异源启动子上游时也具有功能,从而证明抑制因子的作用至少部分是在转录水平上介导的。进一步表征调节miR-375和其他胰腺mirna表达的转录控制机制将有助于更好地了解胰腺的发育和功能。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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3-8 weeks
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