Novel splice variant of mouse insulin2 mRNA: Implications for insulin expression

Panda, Amaresh C.; Kulkarni, Shardul D.; Muralidharan, Bhavana; Bakthavachalu, Baskar; Seshadri, Vasudevan

doi:10.1016/j.febslet.2010.02.020

Cited by 11 publications

(19 citation statements)

References 25 publications

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“…The short 5′UTR splice variant constitutes 75% of the insulin2 mRNA pool, and has an increased translation efficiency [7]. In the present study, we show that miR-196b can specifically target the 5′UTR of insulin2 mRNA (the longer 5′UTR containing a splice variant) and regulates its translation in an Ago2-dependent manner.…”

Section: Introductionsupporting

confidence: 50%

“…We have previously shown that specific factors bind to the insulin 5′UTR with differential efficiency [7]. A specific RNA-protein complex is formed with insulin2 5′UTR and cytoplasmic protein factors, but in case of insulin2-S, the complex formation is reduced.…”

Section: Resultsmentioning

confidence: 99%

“…The physiological relevance of this regulation is still unclear, as insulin2 isoform contributes only about 13% of total Insulin mRNA and is poorly translated when compared to the mouse Insulin1 or the insulin2-S isoform [7]. Thus, under normal physiological conditions, the protein product from this mRNA isoform is less than 10% of the total insulin produced (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The insulin2-5′UTR luciferase and insulin2-S-5′UTR luciferase pcDNA3 constructs were generated as described previously [7].…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The 5′ and 3′un-translated regions (UTR's) of insulin mRNA have been shown to have a role in this translation regulation [4]; [5]. In mouse, two non-allelic genes encode for insulin and specific splice variants from these genes have also been reported [6]; [7]. Some of the splice variants have altered 5′UTR and have differential translation efficiency and hence have been implicated in diabetes [6].…”

Section: Introductionmentioning

confidence: 99%

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miR-196b-Mediated Translation Regulation of Mouse Insulin2 via the 5′UTR

et al. 2014

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The 5′ and the 3′ untranslated regions (UTR) of the insulin genes are very well conserved across species. Although microRNAs (miRNAs) are known to regulate insulin secretion process, direct regulation of insulin biosynthesis by miRNA has not been reported. Here, we show that mouse microRNA miR-196b can specifically target the 5′UTR of the long insulin2 splice isoform. Using reporter assays we show that miR-196b specifically increases the translation of the reporter protein luciferase. We further show that this translation activation is abolished when Argonaute 2 levels are knocked down after transfection with an Argonaute 2-directed siRNA. Binding of miR-196b to the target sequence in insulin 5′UTR causes the removal of HuD (a 5′UTR-associated translation inhibitor), suggesting that both miR-196b and HuD bind to the same RNA element. We present data suggesting that the RNA-binding protein HuD, which represses insulin translation, is displaced by miR-196b. Together, our findings identify a mechanism of post-transcriptional regulation of insulin biosynthesis.

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Section: Introductionsupporting

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The insulin2-5′UTR luciferase and insulin2-S-5′UTR luciferase pcDNA3 constructs were generated as described previously [7].…”

Section: Experimental Methodsmentioning

confidence: 99%