A novel myogenic function residing in the 5′ non-coding region of Insulin receptor substrate-1 (Irs-1) transcript

BMC Cell Biology

Shigetada Teshima-Kondo¹  Takeshi Nikawa¹  Edward M Mills³  Yuushi Okumura²  Katsuya Hirasaka⁴  Ayako Ohno¹  Tomoki Abe¹  Shohei Kohno¹  Kana Aibara¹  Chiaki Yano¹  Chisato Tomida¹  Naoko Yamagishi¹  Hikaru Nagano² 

[1] Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima 770-8503, Japan;Facalty of Nutritional Science, Sagami Women’s University, Sagamihara 252-0383, Japan;Division of Pharmacology/Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas;Graduate school of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan

关键词: Rb;    Myogenic differentiation;    Insulin receptor substrate-1;    Bifunctional RNA;   

Others  :  1151008
DOI  :  10.1186/s12860-015-0054-8

 received in 2014-10-24, accepted in 2015-02-16,  发布年份 2015

【 摘 要 】

Background

There is evidence that several messenger RNAs (mRNAs) are bifunctional RNAs, i.e. RNA transcript carrying both protein-coding capacity and activity as functional non-coding RNA via 5′ and 3′ untranslated regions (UTRs).

Results

In this study, we identified a novel bifunctional RNA that is transcribed from insulin receptor substrate-1 (Irs-1) gene with full-length 5′UTR sequence (FL-Irs-1 mRNA). FL-Irs-1 mRNA was highly expressed only in skeletal muscle tissue. In cultured skeletal muscle C2C12 cells, the FL-Irs-1 transcript functioned as a bifunctional mRNA. The FL-Irs-1 transcript produced IRS-1 protein during differentiation of myoblasts into myotubes; however, this transcript functioned as a regulatory RNA in proliferating myoblasts. The FL-Irs-1 5′UTR contains a partial complementary sequence to Rb mRNA, which is a critical factor for myogenic differentiation. The overexpression of the 5′UTR markedly reduced Rb mRNA expression, and this reduction was fully dependent on the complementary element and was not compensated by IRS-1 protein. Conversely, knockdown of FL-Irs-1 mRNA increased Rb mRNA expression and enhanced myoblast differentiation into myotubes.

Conclusions

Our findings suggest that the FL-Irs-1 transcript regulates myogenic differentiation as a regulatory RNA in myoblasts.

【 授权许可】

   
2015 Nagano et al.; licensee BioMed Central.

【 图 表 】

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